the ncbi pathogen detection pipeline · pdf filethe ncbi pathogen detection pipeline: ......
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The NCBI Pathogen Detection PipelineProviding Freely Available Analysis Reports
to Support Public Health
William KlimkeWhole Genome Sequencing for the Food Industry
Burr Ridge Illinois
NCBI Pathogen Detection Pipeline Submissions and Analysis
NC
BI
Su
bm
issi
on
Po
rta
l
BioSamples
SRA
GenBank
BioProject
NCBI Pathogen Pipeline
Kmer analysis
Genome Assembly
Genome Annotation
Genome Placement
Clustering
SNP analysis
Tree Construction
Reports
QC
US
AU
KA
us
Cli
nic
al
sample_name
organism
strainisolate
Category (attribute_package)
1a) ClinicalHost-associated
1a1) specific_host
1a2) isolation_source
1a3) host-disease
OR
1b) EnvironmentalFoodOther
1b1) isolation_source
collection_date
Geographic location
6a) geo_loc_name
OR
6b) lat_lon
collected by
Where
When
Who
What
minimal metadata
NCBI Biosample ndash Pathogen Template for Metadata
httpssubmitncbinlmnihgovsubsbiosamplehttpswwwncbinlmnihgovbiosampledocshttpwwwncbinlmnihgovprojectsbiosamplevalidatehttpssubmitncbinlmnihgovbiosampletemplatepackage=Pathogencl10ampaction=definitionhttpssubmitncbinlmnihgovbiosampletemplatepackage=Pathogenenv10ampaction=definition
1 Initial partition of isolates within each species by kmer distances
2 Within each partition blast comparison of all pairs of genomes
3 Single linkage clusters with at most 50 SNPs
4 Within clusters SNPs with respect to one reference
5 Generate final SNP list and phylogenetic trees
Filteringbull Base levelbull Repeat bull Density
Problematic genomes are eliminated at various points along the way
SNP pipeline
Iterative density filtering (modification of)Science 2011 Jan 28331(6016)430-4
Density Filtering
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000
SAMN02351384 vs SAMN03093482
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000 3500000
SAMN02900433 vs SAMN02567775
Second run for a sample
cgMLST vs wgMLST for Salmonella
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
NCBI Pathogen Detection Pipeline Submissions and Analysis
NC
BI
Su
bm
issi
on
Po
rta
l
BioSamples
SRA
GenBank
BioProject
NCBI Pathogen Pipeline
Kmer analysis
Genome Assembly
Genome Annotation
Genome Placement
Clustering
SNP analysis
Tree Construction
Reports
QC
US
AU
KA
us
Cli
nic
al
sample_name
organism
strainisolate
Category (attribute_package)
1a) ClinicalHost-associated
1a1) specific_host
1a2) isolation_source
1a3) host-disease
OR
1b) EnvironmentalFoodOther
1b1) isolation_source
collection_date
Geographic location
6a) geo_loc_name
OR
6b) lat_lon
collected by
Where
When
Who
What
minimal metadata
NCBI Biosample ndash Pathogen Template for Metadata
httpssubmitncbinlmnihgovsubsbiosamplehttpswwwncbinlmnihgovbiosampledocshttpwwwncbinlmnihgovprojectsbiosamplevalidatehttpssubmitncbinlmnihgovbiosampletemplatepackage=Pathogencl10ampaction=definitionhttpssubmitncbinlmnihgovbiosampletemplatepackage=Pathogenenv10ampaction=definition
1 Initial partition of isolates within each species by kmer distances
2 Within each partition blast comparison of all pairs of genomes
3 Single linkage clusters with at most 50 SNPs
4 Within clusters SNPs with respect to one reference
5 Generate final SNP list and phylogenetic trees
Filteringbull Base levelbull Repeat bull Density
Problematic genomes are eliminated at various points along the way
SNP pipeline
Iterative density filtering (modification of)Science 2011 Jan 28331(6016)430-4
Density Filtering
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000
SAMN02351384 vs SAMN03093482
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000 3500000
SAMN02900433 vs SAMN02567775
Second run for a sample
cgMLST vs wgMLST for Salmonella
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
sample_name
organism
strainisolate
Category (attribute_package)
1a) ClinicalHost-associated
1a1) specific_host
1a2) isolation_source
1a3) host-disease
OR
1b) EnvironmentalFoodOther
1b1) isolation_source
collection_date
Geographic location
6a) geo_loc_name
OR
6b) lat_lon
collected by
Where
When
Who
What
minimal metadata
NCBI Biosample ndash Pathogen Template for Metadata
httpssubmitncbinlmnihgovsubsbiosamplehttpswwwncbinlmnihgovbiosampledocshttpwwwncbinlmnihgovprojectsbiosamplevalidatehttpssubmitncbinlmnihgovbiosampletemplatepackage=Pathogencl10ampaction=definitionhttpssubmitncbinlmnihgovbiosampletemplatepackage=Pathogenenv10ampaction=definition
1 Initial partition of isolates within each species by kmer distances
2 Within each partition blast comparison of all pairs of genomes
3 Single linkage clusters with at most 50 SNPs
4 Within clusters SNPs with respect to one reference
5 Generate final SNP list and phylogenetic trees
Filteringbull Base levelbull Repeat bull Density
Problematic genomes are eliminated at various points along the way
SNP pipeline
Iterative density filtering (modification of)Science 2011 Jan 28331(6016)430-4
Density Filtering
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000
SAMN02351384 vs SAMN03093482
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000 3500000
SAMN02900433 vs SAMN02567775
Second run for a sample
cgMLST vs wgMLST for Salmonella
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
1 Initial partition of isolates within each species by kmer distances
2 Within each partition blast comparison of all pairs of genomes
3 Single linkage clusters with at most 50 SNPs
4 Within clusters SNPs with respect to one reference
5 Generate final SNP list and phylogenetic trees
Filteringbull Base levelbull Repeat bull Density
Problematic genomes are eliminated at various points along the way
SNP pipeline
Iterative density filtering (modification of)Science 2011 Jan 28331(6016)430-4
Density Filtering
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000
SAMN02351384 vs SAMN03093482
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000 3500000
SAMN02900433 vs SAMN02567775
Second run for a sample
cgMLST vs wgMLST for Salmonella
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Iterative density filtering (modification of)Science 2011 Jan 28331(6016)430-4
Density Filtering
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000
SAMN02351384 vs SAMN03093482
0
50
100
150
200
250
300
0 500000 1000000 1500000 2000000 2500000 3000000 3500000
SAMN02900433 vs SAMN02567775
Second run for a sample
cgMLST vs wgMLST for Salmonella
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Second run for a sample
cgMLST vs wgMLST for Salmonella
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Current status
Listeria (alleleloci thresholds tested at 50 2500)
Salmonella (alleleloci thresholds tested at 100 10000)
(approx frac14 of all genomes in the dataset at the time of analysis for the larger numbers)
ex Salmonella4551 loci when requiring 10 000 genomes to have that loci (more like a core MLST scheme)16920 loci when requiring 100 genomes to have that loci (wgMLST)
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
httpswwwncbinlmnihgovpathogens
NCBI Pathogen Detection Isolates Browser
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
List of organisms is growing - almost 140 000 pathogens are being clustered
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
NCBI Isolates Browser (searchfiltersort ndash links to SNP trees)
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
NCBI SNP Tree Viewer (examine closely related isolates)subtree in red is E coli O121 flour outbreak
outbreak subtree
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
httpswwwcdcgovecoli2016o121-06-16indexhtml
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
NCBIrsquos Role in Combatting Antibiotic Resistance
ldquoCreate a repository of resistant bacterial strains (an ldquoisolate bankrdquo) and maintain a well-curated reference database that describes the characteristics of these strainsrdquo
ldquoDevelop and maintain a national sequence database of resistant pathogensrdquo
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
The Practical Results of AMR efforts at NCBI
With collaborators build database of sequenced isolates with standardized AST metadata (ie accepting submissions of antibiograms) (4098 Samples as of May) httpswwwncbinlmnihgovbiosampleterm=antibiogram[filter])
Collaborators include (CDC WRAIR FDA BampW Broad)
Stable up-to-date database of AMR genes with standardized nomenclatureCollaborators (CARD Lahey experts)RefSeq set released in June 2016 (4004 genesproteins as of May)
httpswwwncbinlmnihgovbioprojectPRJNA313047
Implement and validate tools for identifying AMR genes in new isolates
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
~4K reference antimicrobialresistance genesproteins(released)
550 HMMs for antimicrobial resistance (AMR) proteins(coming soon)
httpswwwncbinlmnihgovbioprojectPRJNA313047
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
123K with encoding an antmicrobial resistance gene (including chromosomal)and 3K with susceptibility tests
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Identification of the fourth US isolate - an E coli encoding mcr-1
bull a stool sample was collected from a pediatric patient with diarrheabull non-Shiga toxin-producing E coli O157 was isolated and sequencedbull the sequence data was uploaded to SRA
NCBI
bull the Pathogen Detection pipeline assembled and annotated the genomebull the antimicrobial resistance module detected an mcr-1 gene encoded by this sample (mcr-1 is a
recently discovered colistin resistance gene that has been found on mobile elements - Liu et al 2016)
bull CDC was notifiedbull CDC published this information recently in MMWR - note it is the fourth isolate in the US to have
been found to encode mcr-1 (Vasquez et al 2016) and the first to have been discovered by the Pathogen Detection system (in all three previous cases the data were not submitted prior to the announcement)
Liu et al 2016 Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China a microbiological and molecular biological study Lancet Infect Dis 16(2)161-8
Vasquez et al 2016 Investigation of Escherichia coli Harboring the mcr-1 Resistance Gene mdash Connecticut 2016 MMWR 65(36)979-980
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Pathogen Detection Isolates Browser can be used to find isolates of extreme interest
pathogens with mobile colistin resistance gene (mcr) and a KPC allele
Klebsiella from Italy from 2014Klebsiella from Brazil from 2016E coli from Brazil from 2014
httpbitly2r8rBkK
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Future Directions in AMR
bull Incorporate efflux pumps cell wall proteins and other genes where allelic variation in core genes determines resistance
bull Incorporate Tb data
bull Improve prediction of resistance to specific antibioticswithin drug classes
bull Working with clinical groups and NIAIDGSCs to improve clinical antibiogram submission process
bull Resolving nomenclature
bull actively working with the AMR community on
bull OXA beta-lactamases
bull aminoglycoside modifying enzymes
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov
Acknowledgements
Richa AgarwalaAzat BadretdinSlava BroverJoshua CherryVyacheslav ChetverninRobert CohenMichael DiCuccioBoris FedorovMike FeldgardenLewis GeerDan HaftLianyi HanWilliam KlimkeAlex KotliarovArjun PrasadEdward RiceKirill Rotmistrovskyy
This research was supported by the Intramural Research Program of the NIH National Library of Medicine httpwwwncbinlmnihgov
National Center for Biotechnology Information ndash National Library of Medicine ndash Bethesda MD 20892 USA
CDCFDACFSANUSDA-FSISPHEFERANIHGRINIAIDWRAIRBroadWadsworthMDH
Stephen SherrySergey ShiryevMartin ShumwayTatiana TatusovaIgor TolstoyChunlin XiaoLeonid ZaslavskyAlexander ZasypkinAlejandro A SchafferLukas WagnerAleksandr Morgulis
David LipmanJames Ostell
pd-helpncbinlmnihgov