we teach microbiology but we learn from … · • in our colons, there are about 1012 ... know the...
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EMERGING ISSUES IN MICROBIAL DIVERSITY
SALT LAKE CITY, MAY 2002
WE TEACHMICROBIOLOGY
BUT WE LEARNFROM MICROBES
SOME PERTINENT COMMENTS
"the microbe always has the last word""all life in the biosphere depends on microbes"
"all microbiology is environmental microbiology"
THE HIDDEN WORLDS OF MICROBIOLOGY• The number of prokaryote cells in the biosphere (but not the universe?) is
estimated to be 6,000,000,000,000,000,000,000,000,000,000 (6 x 1030).• These contain 50% of the earth's carbon, 90% of nitrogen and phosphorus, and
more than 108 species.• In our colons, there are about 1012 bacteria, not all of which have been
identified.• To date, only 1,500 microbes are known to cause disease in humans or animals.
• There are <109 bacteria in 1 gram of soil.
• A gram of soil contains 1,000-5,000 different species of bacteria.
But what of the eukaryotic microbes?Recent studies show a vast hidden diversity of fungi and protists in the biosphere.
SOME APPLICATIONS
FACTORIESFOOD AND FUEL
DISEASE
BIOREMEDIATION
ENZYMES, VECTORS,
PROCESSES (PCR)MICROBES
BIOTERRORISMDRUGS
EVOLUTION
WHY STUDY?
The Limits of LifeDiversity
Cellular Interactions and CommunitiesEvolutionDisease
Microbial PhysiologyBiotechnology and Bioterrorism
LIMITS OF LIFE
Temperature: 4-130?pH: 1-10?
Genetic: 20-78% G+CPressure
Chemical and physical stress
An example of microbes growing under stress:lichens in an extreme environment.Notre Dame, Paris.
DIVERSITY
Microbial ecology of biological nichesMetagenomesUnidentified microbial divisionsSmall eukaryotesUnrealised potential
DIRT TO PAYDIRT
IDENTIFICATION MICROBES APPLICATIONS
(MICROBIAL
CATALOGUE)
(BIOCATALYSIS,BIOTRANSFORMATION)
DIRT
rDNA SEQUENCECATALOGUEMETAGENOME DNA
GENES & PATHWAYS
INTERACTIONSSymbiosis
AntagonismCommensalism
Do all of these responses happen in microbial communities?
THE ROLES OF MICROBES INTHE EVOLUTION OF HIGHER LIFE FORMS
AND THE CONSTANT EVOLUTION OF MICROBES:
MorphogenesisDevelopmental programmes
Regulatory networksPathogenesis
“Why worry about life in space (astrobiology, etc.) when terrestrial microbes can provide clues as to the origins and evolution of eukaryotic differentiation?”
A bacterial mouth!!?(Momma et al. J. Bact. 2000)
HORIZONTAL (LATERAL) GENE TRANSFERHOW CAN IT BE ESTABLISHED?
1. Demonstration in the laboratory or the environment2. Sequence or motif similarity (DNA or protein)3. Islands of distinct base composition4. Nucleic acid hybridisation5. Association with movable elements6. Extrachromosomal association 7. Phenotypic and behavioral similarities
Disease
PathogenesisPrevention
Treatment and Resistance
Know the enemy• Life cycle and ecology of infectious microbes• Evolutionary lineage• Environmental changes associated with infection• Host-range variation• Diagnosis• Mechanisms of host/pathogen interaction• Mechanisms of resistance• Host susceptibility determinants• CELLULAR MICROBIOLOGY!
Cellular microbiology: the interaction of prokaryotes and eukaryotes
ANTIBIOTIC RESISTANCE MECHANISMS 2001
Decreased influx*Increased efflux*
Enzymatic inactivation*Sequestration*
Target modification*Target by-pass*
Target repairTarget amplification
Biofilm formation? Intracellular localisation
*can be acquired by horizontal gene transfer
From where?THAT IS THE QUESTION!
Aspects of Antibiotic Resistance
The clinical problem (Medicine)Why it happened (Human nature)
How it happened (Genetics)Mechanisms (Biochemistry)
Origins (Speculation)Solutions (Politics)
HOW BUGS BECOME ANTIBIOTIC RESISTANT:THE PATHWAY TO BECOMING UNTREATABLE
SENSITIVE INC
REA
SING
SELECTIO
N, STR
ESS, HYPER
MU
TATIO
N
RESISTANCE (low)
M (?)
RESISTANCE (medium)(compensation)
M A
RESISTANCE (high)(compensation)
MULTIDRUGRESISTANCE(compensation) (antagonism)
June 1945:The New York Times
“…..The thoughtlessness of a person playing with penicillin treatment is morally responsible for the death of a man who finally succumbs to infection with the penicillin resistant organism.”
Sir Alexander Fleming
LARGE IS SPECTACULAR, BUTSMALL IS BEAUTIFUL, TOO!
Tantalus Range, B.C.
Genomes, GCs and Small Molecules
Mycoplasma
Chlamydia
Neisseria
Staphylococcus
Mycobacteria
Escherichia
Pseudomonas
Streptomycetes
52
37
66
50
67
75
SPECIALISTSGENERALISTS
Seco
ndar
y M
etab
olite
Pro
duct
ion
42
404 6 82
Genome Size (Mb) (%G+C)
MULTIPLE ACTIVITIES FOR SMALL MOLECULES IN BIOLOGY
Growth inhibitors, allosteric effectors,transcription activators, pheromones,
quorum sensors, insecticides, immunosuppressives, cell-signalling,
hormone analogs, plant growth regulators,surfactants, antivirals, antitumour agents,herbicides, antiparasitics, antihelminthics,antifungals, cholesterol-lowering agents,
and enzyme inhibitors
Signaling molecule diversity (I)
O
O
H
N
H
OO H
OH O
OCH3
O
O
Br
Br
Br
HN
CH
C
H2 C
O
O
CO
HO
HNCHC
CH2
O
O
S
NH
CHC
CH
OOCH3
CH2
H3 C
NH
CH
C
CH2
OH
2CS
CH3
HN
CH
CCH
2O
O
NH
CHC
CH2
O
O
HO
NH
CHC
CH
O
O
HO
CH3
NH2
CH
CH
2 C
O
O
HO
NH2
CH
C
H2C
O
O
H2C
C
HO
O
HN CH
C
H2C
O
O
CH2
H2C NH
C NH2
HN
HN CH
C
H
O
O HN CH
C
H2C
O
O
CH2
S CH3
HN CH
C
CH
OH
O
HO
CH3
AgrD1 thiolactone signaling peptide from Staphylococcus aureus
3-hydroxypalmitic acid ester from Ralstonia solanacearum
V. harveyi N-(β-hydroxy-butyryl)-L-homoserine lactone
Inhibitory furanonefrom marine algae Delisea pulchra
Bacillus subtilis CSF (ERGMT)
Signaling molecule diversity (II)
from Pseudomonas aeruginosa:O
O
H
N
H
O
O
OH
H
N
OO
N-butyryl homoserine lactone (PAI-2)N-(3-oxo-dodecanoyl)-L-
homoserine lactone (PAI-1)
N
NH
O
O
H
H OH
NH
NH
O
O
HH
HN
OOH
H
2-hydroxy-3 heptyl-4-quinolone (PQS) cyclo (L-Pro-L-Tyr)cyclo (∆ Ala-L-Val)
Cyclic dipeptides
Role of antibiotics in the development of resistance
SelectionPhage
inductionInduced mutagenesis
MutagenicityVirulence ANTIBIOTICS
Gene transfer Transposition
Gene delivery Biofilms
Biology is much more thanDNA, RNA,
proteins and membranes!
Perlman's rules (1980)always rightyour frienda sensitive partner
The microorganism is
There are NO stupid microorganisms.
canMicroorganisms do anything.
will
smarter than chemists, Microorganisms are wiser than engineers,
more energetic than etc.
If you take care of your microbial friends, they will take care of your future and you will live happily ever after.
"It is essential that microbiology be perceived and practiced in a way consistent with the natural order of things; microbes are the base for and sustain all other life on this planet. Let us reorganize all of biology around microbiology."
Carl R. Woese 1994
The genealogy of 'omic' sciences(or everyone wants their own "-omic")
GENOMICS
FUNCTIONAL GENOMICS
GNOMICSMETAGENOMICSENTEROMICS VIROMICS
METABOLOMICSPHYSIOMICS
PROTEOMICS
RNOMICS
ARRAYOMICS(TRANSCRIPTOMICS)
ARCHEOMICS
TRANSPOSOMICS
BIOGEOMICS
SYSTOMICSGLYCOMICS