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 S1  Journal: Environment International Supplementary materials of the article: Large-scale biogeographical patterns of bacterial antibiotic resistome in the waterbodies of China Lemian Liu a,b,# , Jian-Qiang Su a,# , Yunyan Guo a,c,# , David M. Wilkinson d , Zhengwen Liu e , Yong-Guan Zhu a , Jun Yang a, * a Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, People’s Republic of China b College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, People’s Republic of China c University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China d School of Life Sciences, University of Lincoln, Lincoln LN6 7TS, UK. e State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, People’s Republic of China # These authors contributed equally to this work. *Corresponding author: Jun Yang; E-mail: [email protected] This supplementary information contains: 36 Pages 6 Figures 11 Tables 47 References

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Page 1: Large-scale biogeographical patterns of bacterial ... · catA1 GGGTGAGTTTCACCAGTTTTGATT CACCTTGTCGCCTTGCGTATA FCA Antibiotic deactivate √ catB3 GCACTCGATGCCTTCCAAAA AGAGCCGATCCAAACGTCAT

 

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Journal: Environment International

Supplementary materials of the article:

Large-scale biogeographical patterns of bacterial

antibiotic resistome in the waterbodies of China

Lemian Liu a,b,#, Jian-Qiang Su a,#, Yunyan Guo a,c,#, David M. Wilkinson d,

Zhengwen Liu e, Yong-Guan Zhu a, Jun Yang a,*

a Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese

Academy of Sciences, Xiamen 361021, People’s Republic of China b College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, People’s

Republic of China c University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China d School of Life Sciences, University of Lincoln, Lincoln LN6 7TS, UK. e State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and

Limnology, Chinese Academy of Sciences, Nanjing 210008, People’s Republic of China

# These authors contributed equally to this work.

*Corresponding author: Jun Yang; E-mail: [email protected]

This supplementary information contains: 36 Pages 6 Figures 11 Tables 47 References

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Fig. S1 Absolute abundance (108 copies/L, Left) and normalized abundance (MGEs/16S rRNA

gene copy number, right) of mobile genetic elements (MGEs) in five geographical regions across

China (green - South and Central China, red - North China; see Materials and methods, data are

expressed as mean ± s.e.). FJ (included 5 reservoirs) - Fujian province, southeast China; CJ (9

lakes) - the lower and middle reaches of Changjiang River, China; ECC (6 lakes) - east central

China, IM (13 lakes) - Inner Mongolia, north China; NEC (9 lakes) - northeast China. One-way

ANOVA was used to denote the differences among regions.

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Fig. S2 Antibiotic resistance genes (ARGs) profile of natural lakes and reservoirs from five

regions across China. The percentage of ARGs conferring resistance to a specific class of

antibiotics (left). The percentage of ARGs with different resistance mechanisms(right). FCA -

fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol; MLSB - macrolide,

lincosamide and streptogramin; Others - the ARGs conferring resistance to other antibiotic classes,

including bacitracin, fosfomycin, imipenem, lantibiotic, nitroimidazole, pyrazinamide, triclosan,

trimethoprim and unknown. FJ (included 5 reservoirs) - Fujian province, southeast China; CJ (9

lakes) - the lower and middle reaches of Changjiang River, China; ECC (6 lakes) - east central

China, IM (13 lakes) - Inner Mongolia, north China; NEC (9 lakes) - northeast China.

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Fig. S3 Absolute abundance (107 copies/L, Left) and normalized abundance (ARGs/16S rRNA

gene copy number, right) of ARGs in five geographical regions across China (data are expressed

as mean ± s.e.). FJ (included 5 reservoirs) - Fujian province, southeast China; CJ (9 lakes) - the

lower and middle reaches of Changjiang River, China; ECC (6 lakes) - east central China, IM (13

lakes) - Inner Mongolia, north China; NEC (9 lakes) - northeast China. Others - the ARGs

conferring resistance to other antibiotic classes, including bacitracin, fosfomycin, imipenem,

lantibiotic, nitroimidazole, pyrazinamide, triclosan, trimethoprim and unknown.

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Fig. S4 Richness of ARGs in five geographical regions across China (data are expressed as mean

± s.e.). FJ (included 5 reservoirs) - Fujian province, southeast China; CJ (9 lakes) - the lower and

middle reaches of Changjiang River, China; ECC (6 lakes) - east central China, IM (13 lakes) -

Inner Mongolia, north China; NEC (9 lakes) - northeast China. Others - the ARGs conferring

resistance to other antibiotic classes, including bacitracin, fosfomycin, imipenem, lantibiotic,

nitroimidazole, pyrazinamide, triclosan, trimethoprim and unknown.

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Fig. S5 Spearman correlations showing the relationships between the number of sites which an

antibiotic resistance gene was detected and log10 transformed absolute abundance (the number of

ARGs per litre water) (A) or log10 transformed normalized abundance (ARG/16S rRNA gene copy

number) of that gene (B). Each black dot indicates an antibiotic resistance gene.

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Fig. S6. Network analysis revealing the co-occurrence patterns between ARGs and bacterial families. The nodes were coloured according to ARG types and bacterial family (n = 41, see Materials and methods).

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Table S1 Sample information of 42 lakes and reservoirs for this study Lake/reservoir name Region Lat. (°N) Long. (°E) Province Hubian R. FJ 24.50 118.15 Fujian Bantou R. FJ 24.67 118.02 Fujian Shidou R. FJ 24.69 118.01 Fujian Tingxi R. FJ 24.80 118.14 Fujian Dongzhen R. FJ 25.48 118.94 Fujian Poyang L. CJ 28.99 116.21 Jiangxi Longgan L. CJ 29.94 116.17 Hubei & Anhui Taibai L. CJ 29.96 115.80 Hubei Liangzi L. CJ 30.24 114.51 Hubei Shengjin L. CJ 30.39 117.04 Anhui Nanyi L. CJ 31.12 118.98 Anhui Taihu L. CJ 31.22 120.14 Jiangsu, Zhejiang and

Shanghai Gucheng L. CJ 31.28 118.92 Jiangsu Shijiu L. CJ 31.47 118.89 Anhui & Jiangsu Hongze L. ECC 33.28 118.73 Jiangsu Luoma L. ECC 34.05 118.22 Jiangsu Weishan L. ECC 34.64 117.28 Shandong & Jiangsu Dongping L. ECC 35.97 116.19 Shandong Hengshui L. ECC 37.62 115.63 Heibei Baiyangdian L. ECC 38.94 115.98 Heibei Yuehai L. IM 38.56 106.20 Ningxia Shahu L. IM 38.83 106.36 Ningxia Xinhai L. IM 38.99 106.40 Ningxia Daihai L. IM 40.57 112.67 Inner Mongolia Hasuhai L. IM 40.61 110.97 Inner Mongolia Donghaizi L. IM 40.63 107.00 Inner Mongolia Wuliangsuhai L. IM 40.87 108.79 Inner Mongolia Quansanhaizi L. IM 41.07 107.87 Inner Mongolia Shenglihaizi L. IM 41.12 107.83 Inner Mongolia Bei’er L. IM 47.93 117.70 Inner Mongolia Wulanpao L. IM 48.36 117.52 Inner Mongolia Hulun L. IM 49.12 117.54 Inner Mongolia Huhenuo’er L. IM 49.30 119.23 Inner Mongolia Xinmiaopao L. NEC 45.21 124.45 Jiling Kulipao L. NEC 45.37 124.50 Jiling Xinhuangpao L. NEC 45.63 123.76 Jiling Yueliangpao L. NEC 45.74 124.00 Jiling Lamasipao L. NEC 46.29 124.10 Heilongjiang Amutapao L. NEC 46.61 124.06 Heilongjiang Dongxintunnanpao L. NEC 46.81 124.26 Heilongjiang Qijiapao L. NEC 46.82 124.28 Heilongjiang Tianhu L. NEC 46.87 124.40 Heilongjiang

FJ (included 5 reservoirs) - Fujian province, southeast China; CJ (9 lakes) - the lower and middle reaches of Changjiang River, China; ECC (6 lakes) - east central China, IM (13 lakes) - Inner Mongolia, north China; NEC (9 lakes) - northeast China.

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Table S2 Primer sets used in this study and their target classification (Su, et al., 2015; Zhu, et al., 2013) Gene name Forward primer Reverse primer Classification Mechanism ARDB CARD Other Source

16S rRNA GGGTTGCGCTCGTTGC ATGGYTGTCGTCAGCTCGTG na na

aac CCCTGCGTTGTGGCTATGT TTGGCCACGCCAATCC Aminoglycoside Antibiotic deactivate √ √

aac(6')I1 GACCGGATTAAGGCCGATG CTTGCCTTGATATTCAGTTTTTATAACCA Aminoglycoside Antibiotic deactivate √ √

aac(6')-Ib(aka aacA4)-01 GTTTGAGAGGCAAGGTACCGTAA GAATGCCTGGCGTGTTTGA Aminoglycoside Antibiotic deactivate √ √

aac(6')-Ib(aka aacA4)-02 CGTCGCCGAGCAACTTG CGGTACCTTGCCTCTCAAACC Aminoglycoside Antibiotic deactivate √ √

aac(6')-Ib(aka aacA4)-03 AGAAGCACGCCCGACACTT GCTCTCCATTCAGCATTGCA Aminoglycoside Antibiotic deactivate √ √

aac(6')-II CGACCCGACTCCGAACAA GCACGAATCCTGCCTTCTCA Aminoglycoside Antibiotic deactivate √ √

aac(6')-Iy GCTTTGCGGATGCCTCAAT GGAGAACAAAAATACCTTCAAGGAAA Aminoglycoside Antibiotic deactivate √ √

aacA/aphD AGAGCCTTGGGAAGATGAAGTTT TTGATCCATACCATAGACTATCTCATCA Aminoglycoside Antibiotic deactivate √ √

aacC CGTCACTTATTCGATGCCCTTAC GTCGGGCGCGGCATA Aminoglycoside Antibiotic deactivate √ √

aacC1 GGTCGTGAGTTCGGAGACGTA GCAAGTTCCCGAGGTAATCG Aminoglycoside Antibiotic deactivate √ √

aacC2 ACGGCATTCTCGATTGCTTT CCGAGCTTCACGTAAGCATTT Aminoglycoside Antibiotic deactivate √ √

aacC4 CGGCGTGGGACACGAT AGGGAACCTTTGCCATCAACT Aminoglycoside Antibiotic deactivate √ √

aadA-01 GTTGTGCACGACGACATCATT GGCTCGAAGATACCTGCAAGAA Aminoglycoside Antibiotic deactivate √ √

aadA-02 CGAGATTCTCCGCGCTGTA GCTGCCATTCTCCAAATTGC Aminoglycoside Antibiotic deactivate √ √

aadA1 AGCTAAGCGCGAACTGCAAT TGGCTCGAAGATACCTGCAA Aminoglycoside Antibiotic deactivate √ √

aadA-1-01 AAAAGCCCGAAGAGGAACTTG CATCTTTCACAAAGATGTTGCTGTCT Aminoglycoside Antibiotic deactivate √ √

aadA-1-02 CGGAATTGAAAAAACTGATCGAA ATACCGGCTGTCCGTCATTT Aminoglycoside Antibiotic deactivate √ √

aadA2-01 ACGGCTCCGCAGTGGAT GGCCACAGTAACCAACAAATCA Aminoglycoside Antibiotic deactivate √ √

aadA2-02 CTTGTCGTGCATGACGACATC TCGAAGATACCCGCAAGAATG Aminoglycoside Antibiotic deactivate √ √

aadA2-03 CAATGACATTCTTGCGGGTATC GACCTACCAAGGCAACGCTATG Aminoglycoside Antibiotic deactivate √ √

aadA5-01 ATCACGATCTTGCGATTTTGCT CTGCGGATGGGCCTAGAAG Aminoglycoside Antibiotic deactivate

aadA5-02 GTTCTTGCTCTTGCTCGCATT GATGCTCGGCAGGCAAAC Aminoglycoside Antibiotic deactivate

aadA9-01 CGCGGCAAGCCTATCTTG CAAATCAGCGACCGCAGACT Aminoglycoside Antibiotic deactivate √ √

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aadA9-02 GGATGCACGCTTGGATGAA CCTCTAGCGGCCGGAGTATT Aminoglycoside Antibiotic deactivate √ √

aadD CCGACAACATTTCTACCATCCTT ACCGAAGCGCTCGTCGTATA Aminoglycoside Antibiotic deactivate √ √

aadE TACCTTATTGCCCTTGGAAGAGTTA GGAACTATGTCCCTTTTAATTCTACAATCT Aminoglycoside Antibiotic deactivate √ √

aph TTTCAGCAAGTGGATCATGTTAAAAT CCAAGCTGTTTCCACTGTTTTTC Aminoglycoside Antibiotic deactivate

Zhu et al. 2013

aph(2')-Id-01 TGAGCAGTATCATAAGTTGAGTGAAAAG GACAGAACAATCAATCTCTATGGAATG Aminoglycoside Antibiotic deactivate

aph(2')-Id-02 TAAGGATATACCGACAGTTTTGGAAA TTTAATCCCTCTTCATACCAATCCATA Aminoglycoside Antibiotic deactivate

aph6ia CCCATCCCATGTGTAAGGAAA GCCACCGCTTCTGCTGTAC Aminoglycoside Antibiotic deactivate √ √

aphA1(aka kanR) TGAACAAGTCTGGAAAGAAATGCA CCTATTAATTTCCCCTCGTCAAAAA Aminoglycoside Antibiotic deactivate √ √

sat4 GAATGGGCAAAGCATAAAAACTTG CCGATTTTGAAACCACAATTATGATA Aminoglycoside Antibiotic deactivate

spcN-01 AAAAGTTCGATGAAACACGCCTAT TCCAGTGGTAGTCCCCGAATC Aminoglycoside Antibiotic deactivate

spcN-02 CAGAATCTTCCTGAAAAGTTTGATGAA CGCAGACACGCCGAATC Aminoglycoside Antibiotic deactivate

str AATGAGTTTTGGAGTGTCTCAACGTA AATCAAAACCCCTATTAAAGCCAAT Aminoglycoside Antibiotic deactivate √ √

strA CCGGTGGCATTTGAGAAAAA GTGGCTCAACCTGCGAAAAG Aminoglycoside Antibiotic deactivate √ √

strB GCTCGGTCGTGAGAACAATCT CAATTTCGGTCGCCTGGTAGT Aminoglycoside Antibiotic deactivate √ √

ampC/blaDHA TGGCCGCAGCAGAAAGA CCGTTTTATGCACCCAGGAA Beta-Lactamase Antibiotic deactivate

Zhu et al. 2013

ampC-01 TGGCGTATCGGGTCAATGT CTCCACGGGCCAGTTGAG Beta-Lactamase Antibiotic deactivate √

ampC-02 GCAGCACGCCCCGTAA TGTACCCATGATGCGCGTACT Beta-Lactamase Antibiotic deactivate √

ampC-04 TCCGGTGACGCGACAGA CAGCACGCCGGTGAAAGT Beta-Lactamase Antibiotic deactivate √

ampC-05 CTGTTCGAGCTGGGTTCTATAAGTAAA CAGTATCTGGTCACCGGATCGT Beta-Lactamase Antibiotic deactivate √

ampC-06 CCGCTCAAGCTGGACCATAC CCATATCCTGCACGTTGGTTT Beta-Lactamase Antibiotic deactivate √

ampC-07 CCGCCCAGAGCAAGGACTA GCTCGACTTCACGCCGTAAG Beta-Lactamase Antibiotic deactivate √

ampC-09 CAGCCGCTGATGAAAAAATATG CAGCGAGCCCACTTCGA Beta-Lactamase Antibiotic deactivate √

bla1 GCAAGTTGAAGCGAAAGAAAAGA TACCAGTATCAATCGCATATACACCTAA Beta-Lactamase Antibiotic deactivate √

bla-ACC-1 CACACAGCTGATGGCTTATCTAAAA AATAAACGCGATGGGTTCCA Beta-Lactamase Antibiotic deactivate √ √

blaCMY CCGCGGCGAAATTAAGC GCCACTGTTTGCCTGTCAGTT Beta-Lactamase Antibiotic deactivate √ √

blaCMY2-01 AAAGCCTCAT GGGTGCATAAA ATAGCTTTTGTTTGCCAGCATCA Beta-Lactamase Antibiotic deactivate √ √

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blaCMY2-02 GCGAGCAGCCTGAAGCA CGGATGGGCTTGTCCTCTT Beta-Lactamase Antibiotic deactivate √ √

blaCTX-M-01 GGAGGCGTGACGGCTTTT TTCAGTGCGATCCAGACGAA Beta-Lactamase Antibiotic deactivate √ √

blaCTX-M-02 GCCGCGGTGCTGAAGA ATCGGATTATAGTTAACCAGGTCAGATTT Beta-Lactamase Antibiotic deactivate √ √

blaCTX-M-03 CGATACCACCACGCCGTTA GCATTGCCCAACGTCAGATT Beta-Lactamase Antibiotic deactivate √ √

blaCTX-M-04 CTTGGCGTTGCGCTGAT CGTTCATCGGCACGGTAGA Beta-Lactamase Antibiotic deactivate √ √

blaCTX-M-05 GCGATAACGTGGCGATGAAT GTCGAGACGGAACGTTTCGT Beta-Lactamase Antibiotic deactivate √ √

blaCTX-M-06 CACAGTTGGTGACGTGGCTTAA CTCCGCTGCCGGTTTTATC Beta-Lactamase Antibiotic deactivate √ √

blaGES GCAATGTGCTCAACGTTCAAG GTGCCTGAGTCAATTCTTTCAAAG Beta-Lactamase Antibiotic deactivate √ √

blaIMP-01 AACACGGTTTGGTGGTTCTTGTA GCGCTCCACAAACCAATTG Beta-Lactamase Antibiotic deactivate √

blaPSE TTGTGACCTATTCCCCTGTAATAGAA TGCGAAGCACGCATCATC Beta-Lactamase Antibiotic deactivate √ √

bla-L1 CACCGGGTTACCAGCTGAAG GCGAAGCTGCGCTTGTAGTC Beta-Lactamase Antibiotic deactivate √

blaMOX/blaCMY CTATGTCAATGTGCCGAAGCA GGCTTGTCCTCTTTCGAATAGC Beta-Lactamase Antibiotic deactivate √

blaIMP-02 AAGGCAGCATTTCCTCTCATTTT GGATAGATCGAGAATTAAGCCACTCT Beta-Lactamase Antibiotic deactivate √

blaOCH GGCGACTTGCGCCGTAT TTTTCTGCTCGGCCATGAG Beta-Lactamase Antibiotic deactivate √

blaOKP GCCGCCATCACCATGAG GGTGACGTTGTCACCGATCTG Beta-Lactamase Antibiotic deactivate √ √

blaOXA1/blaOXA30 CGGATGGTTTGAAGGGTTTATTAT TCTTGGCTTTTATGCTTGATGTTAA Beta-Lactamase Antibiotic deactivate √ √

blaOXA10-01 CGCAATTATCGGCCTAGAAACT TTGGCTTTCCGTCCCATTT Beta-Lactamase Antibiotic deactivate √ √

blaOXA10-02 CGCAATTATCGGCCTAGAAACT TTGGCTTTCCGTCCCATTT Beta-Lactamase Antibiotic deactivate √ √

blaOXY CGTTCAGGCGGCAGGTT GCCGCGATATAAGATTTGAGAATT Beta-Lactamase Antibiotic deactivate √

blaPAO CGCCGTACAACCGGTGAT GAAGTAATGCGGTTCTCCTTTCA Beta-Lactamase Antibiotic deactivate √

blaPER TGCTGGTTGCTGTTTTTGTGA CCTGCGCAATGATAGCTTCAT Beta-Lactamase Antibiotic deactivate √

blaROB GCAAAGGCATGACGATTGC CGCGCTGTTGTCGCTAAA Beta-Lactamase Antibiotic deactivate √ √

blaSFO CCGCCGCCATCCAGTA GGGCCGCCAAGATGCT Beta-Lactamase Antibiotic deactivate

Zhu et al. 2013

blaSHV-01 TCCCATGATGAGCACCTTTAAA TTCGTCACCGGCATCCA Beta-Lactamase Antibiotic deactivate √ √

blaSHV-02 CTTTCCCATGATGAGCACCTTT TCCTGCTGGCGATAGTGGAT Beta-Lactamase Antibiotic deactivate √ √

blaTEM AGCATCTTACGGATGGCATGA TCCTCCGATCGTTGTCAGAAGT Beta-Lactamase Antibiotic deactivate √ √

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blaTLA ACACTTTGCCATTGCTGTTTATGT TGCAAATTTCGGCAATAATCTTT Beta-Lactamase Antibiotic deactivate

Zhu et al. 2013

blaVEB CCCGATGCAAAGCGTTATG GAAAGATTCCCTTTATCTATCTCAGACAA Beta-Lactamase Antibiotic deactivate √

blaVIM GCACTTCTCGCGGAGATTG CGACGGTGATGCGTACGTT Beta-Lactamase Antibiotic deactivate √

blaZ GGAGATAAAGTAACAAATCCAGTTAGATATGA TGCTTAATTTTCCATTTGCGATAAG Beta-Lactamase Antibiotic deactivate √

cepA AGTTGCGCAGAACAGTCCTCTT TCGTATCTTGCCCGTCGATAAT Beta-Lactamase Antibiotic deactivate √ √

cfiA GCAGCGTTGCTGGACACA GTTCGGGATAAACGTGGTGACT Beta-Lactamase Antibiotic deactivate √ √

cfxA TCATTCCTCGTTCAAGTTTTCAGA TGCAGCACCAAGAGGAGATGT Beta-Lactamase Antibiotic deactivate √ √

cphA-01 GCGAGCTGCACAAGCTGAT CGGCCCAGTCGCTCTTC Beta-Lactamase Antibiotic deactivate √

cphA-02 GTGCTGATGGCGAGTTTCTG GGTGTGGTAGTTGGTGTTGATCAC Beta-Lactamase Antibiotic deactivate √

fox5 GGTTTGCCGCTGCAGTTC GCGGCCAGGTGACCAA Beta-Lactamase Antibiotic deactivate

ndm-1 ATTAGCCGCTGCATTGAT CATGTCGAGATAGGAAGTG Beta-Lactamase Antibiotic deactivate

mecA GGTTACGGACAAGGTGAAATACTGAT TGTCTTTTAATAAGTGAGGTGCGTTAATA Beta-Lactamase cellular protection √ √

pbp CCGGTGCCATTGGTTTAGA AAAATAGCCGCCCCAAGATT Beta-Lactamase cellular protection

Zhu et al. 2013

pbp2x TTTCATAAGTATCTGGACATGGAAGAA CCAAAGGAAACTTGCTTGAGATTAG Beta-Lactamase cellular protection √ √

Pbp5 GGCGAACTTCTAATTAATCCTATCCA CGCCGATGACATTCTTCTTATCTT Beta-Lactamase cellular protection

Fontana et al. 1985

penA AGACGGTAACGTATAACTTTTTGAAAGA GCGTGTAGCCGGCAATG Beta-Lactamase cellular protection √ √

imiR CCGGACTAGAGCTTCATGTAAGC CCCACGCGGTACTCTTGTAAA Beta-Lactamase Other/Unknown

Norgan et al. 2016

catA1 GGGTGAGTTTCACCAGTTTTGATT CACCTTGTCGCCTTGCGTATA FCA Antibiotic deactivate √

catB3 GCACTCGATGCCTTCCAAAA AGAGCCGATCCAAACGTCAT FCA Antibiotic deactivate √ √

catB8 CACTCGACGCCTTCCAAAG CCGAGCCTATCCAGACATCATT FCA Antibiotic deactivate √ √

cfr GCAAAATTCAGAGCAAGTTACGAA AAAATGACTCCCAACCTGCTTTAT FCA Antibiotic deactivate

Kehrenberg & Schwarz 2006

cmlA1-01 TAGGAAGCATCGGAACGTTGAT CAGACCGAGCACGACTGTTG FCA Efflux pump √ √

cmlA1-02 AGGAAGCATCGGAACGTTGA ACAGACCGAGCACGACTGTTG FCA Efflux pump √ √

cmx(A) GCGATCGCCATCCTCTGT TCGACACGGAGCCTTGGT FCA Efflux pump

Su et al. 2015

floR ATTGTCTTCACGGTGTCCGTTA CCGCGATGTCGTCGAACT FCA Efflux pump √ √

qnrA AGGATTTCTCACGCCAGGATT CCGCTTTCAATGAAACTGCAA FCA cellular protection √ √ Heir et al., 1998

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ereA CCTGTGGTACGGAGAATTCATGT ACCGCATTCGCTTTGCTT MLSB Antibiotic deactivate √ √

ereB GCTTTATTTCAGGAGGCGGAAT TTTTAAATGCCACAGCACAGAATC MLSB Antibiotic deactivate √ √

lnuA-01 TGACGCTCAACACACTCAAAAA TTCATGCTTAAGTTCCATACGTGAA MLSB Antibiotic deactivate √ √

lnuB-01 TGAACATAATCCCCTCGTTTAAAGAT TAATTGCCCTGTTTCATCGTAAATAA MLSB Antibiotic deactivate √ √

lnuB-02 AAAGGAGAAGGTGACCAATACTCTGA GGAGCTACGTCAAACAACCAGTT MLSB Antibiotic deactivate √ √

lnuC TGGTCAATATAACAGATGTAAACCAGATTT CACCCCAGCCACCATCAA MLSB Antibiotic deactivate

mphA-01 CTGACGCGCTCCGTGTT GGTGGTGCATGGCGATCT MLSB Antibiotic deactivate √ √

mphA-02 TGATGACCCTGCCATCGA TTCGCGAGCCCCTCTTC MLSB Antibiotic deactivate √ √

mphB CGCAGCGCTTGATCTTGTAG TTACTGCATCCATACGCTGCTT MLSB Antibiotic deactivate √ √

mphC CGTTTGAAGTACCGAATTGGAAA GCTGCGGGTTTGCCTGTA MLSB Antibiotic deactivate √ √

vatB-01 GGAAAAAGCAACTCCATCTCTTGA TCCTGGCATAACAGTAACATTCTGA MLSB Antibiotic deactivate √ √

vatB-02 TTGGGAAAAAGCAACTCCATCT CAATCCACACATCATTTCCAACA MLSB Antibiotic deactivate √ √

vatC-01 CGGAAATTGGGAACGATGTT GCAATAATAGCCCCGTTTCCTA MLSB Antibiotic deactivate √ √

vatC-02 CGATGTTTGGATTGGACGAGAT GCTGCAATAATAGCCCCGTTT MLSB Antibiotic deactivate √ √

vatE-01 GGTGCCATTATCGGAGCAAAT TTGGATTGCCACCGACAAT MLSB Antibiotic deactivate √ √

vatE-02 GACCGTCCTACCAGGCGTAA TTGGATTGCCACCGACAATT MLSB Antibiotic deactivate √ √

vgb-01 AGGGAGGGTATCCATGCAGAT ACCAAATGCGCCCGTTT MLSB Antibiotic deactivate √ √

vgbB-01 CAGCCGGATTCTGGTCCTT TACGATCTCCATTCAATTGGGTAAA MLSB Antibiotic deactivate √ √

vgbB-02 ATACGAGCTGCCTAATAAAGGATCTT TGTGAACCACAGGGCATTATCA MLSB Antibiotic deactivate √ √

erm(34) GCGCGTTGACGACGATTT TGGTCATACTCGACGGCTAGAAC MLSB cellular protection

erm(35) TTGAAAACGATGTTGCATTAAGTCA TCTATAATCACAACTAACCACTTGAACGT MLSB cellular protection

erm(36) GGCGGACCGACTTGCAT TCTGCGTTGACGACGGTTAC MLSB cellular protection

ermA TTGAGAAGGGATTTGCGAAAAG ATATCCATCTCCACCATTAATAGTAAACC MLSB cellular protection √ √

ermA/ermTR ACATTTTACCAAGGAACTTGTGGAA GTGGCATGACATAAACCTTCATCA MLSB cellular protection √ √

ermB TAAAGGGCATTTAACGACGAAACT TTTATACCTCTGTTTGTTAGGGAATTGAA MLSB cellular protection √ √

ermC TTTGAAATCGGCTCAGGAAAA ATGGTCTATTTCAATGGCAGTTACG MLSB cellular protection √ √

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S14  

ermF CAGCTTTGGTTGAACATTTACGAA AAATTCCTAAAATCACAACCGACAA MLSB cellular protection √ √

ermJ/ermD GGACTCGGCAATGGTCAGAA CCCCGAAACGCAATATAATGTT MLSB cellular protection √ √

ermK-01 GTTTGATATTGGCATTGTCAGAGAAA ACCATTGCCGAGTCCACTTT MLSB cellular protection

ermK-02 GAGCCGCAAGCCCCTTT GTGTTTCATTTGACGCGGAGTAA MLSB cellular protection

ermT-01 GTTCACTAGCACTATTTTTAATGACAGAAGT GAAGGGTGTCTTTTTAATACAATTAACGA MLSB cellular protection √ √

ermT-02 GTAAAATCCCTAGAGAATACTTTCATCCA TGAGTGATATTTTTGAAGGGTGTCTT MLSB cellular protection √ √

ermX GCTCAGTGGTCCCCATGGT ATCCCCCCGTCAACGTTT MLSB cellular protection √ √

ermY TTGTCTTTGAAAGTGAAGCAACAGT TAACGCTAGAGAACGATTTGTATTGAG MLSB cellular protection √ √

pikR1 TCGACATGCGTGACGAGATT CCGCGAATTAGGCCAGAA MLSB cellular protection

Almutairi et al. 2015

pikR2 TCGTGGGCCAGGTGAAGA TTCCCCTTGCCGGTGAA MLSB cellular protection

Almutairi et al. 2015

carB GGAGTGAGGCTGACCGTAGAAG ATCGGCGAAACGCACAAA MLSB Efflux pump

Zhu et al. 2013

lmrA-01 TCGACGTGACCGTAGTGAACA CGTGACTACCCAGGTGAGTTGA MLSB Efflux pump, cellular protection1 √ √

matA/mel TAGTAGGCAAGCTCGGTGTTGA CCTGTGCTATTTTAAGCCTTGTTTCT MLSB Efflux pump

mefA CCGTAGCATTGGAACAGCTTTT AAACGGAGTATAAGAGTGCTGCAA MLSB Efflux pump √ √

msrA-01 CTGCTAACACAAGTACGATTCCAAAT TCAAGTAAAGTTGTCTTACCTACACCATT MLSB Efflux pump √ √

msrC-01 TCAGACCGGATCGGTTGTC CCTATTTTTTGGAGTCTTCTCTCTAATGTT MLSB Efflux pump

oleC CCCGGAGTCGATGTTCGA GCCGAAGACGTACACGAACAG MLSB Efflux pump

vgaA-01 CGAGTATTGTGGAAAGCAGCTAGTT CCCGTACCGTTAGAGCCGATA MLSB Efflux pump √ √

vgaA-02 GACGGGTATTGTGGAAAGCAA TTTCCTGTACCATTAGATCCGATAATT MLSB Efflux pump √ √

acrA-01 CAACGATCGGACGGGTTTC TGGCGATGCCACCGTACT Multidrug Efflux pump √ √

acrA-02 GGTCTATCACCCTACGCGCTATC GCGCGCACGAACATACC Multidrug Efflux pump √ √

acrA-03 CAGACCCGCATCGCATATT CGACAATTTCGCGCTCATG Multidrug Efflux pump √ √

acrA-04 TACTTTGCGCGCCATCTTC CGTGCGCGAACGAACAT Multidrug Efflux pump √ √

acrA-05 CGTGCGCGAACGAACA ACTTTGCGCGCCATCTTC Multidrug Efflux pump √ √

acrB-01 AGTCGGTGTTCGCCGTTAAC CAAGGAAACGAACGCAATACC Multidrug Efflux pump √ √

acrF GCGGCCAGGCACAAAA TACGCTCTTCCCACGGTTTC Multidrug Efflux pump

√ Lau et al., 200

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S15  

acrR-01 GCGCTGGAGACACGACAAC GCCTTGCTGCGAGAACAAA Multidrug Efflux pump

√ Pradel et al., 2002

acrR-02 GATGATACCCCCTGCTGTGAGA ACCAAACAAGAAGCGCAAGAA Multidrug Efflux pump

√ Pradel et al., 2002

adeA CAGTTCGAGCGCCTATTTCTG CGCCCTGACCGACCAAT Multidrug Efflux pump √ √

ceoA ATCAACACGGACCAGGACAAG GGAAAGTCCGCTCACGATGA Multidrug Efflux pump √ √

cmeA GCAGCAAAGAAGAAGCACCAA AGCAGGGTAAGTAAAACTAAGTGGTAAATCT Multidrug Efflux pump

cmr CGGCATCGTCAGTGGAATT CGGTTCCGAAAAAGATGGAA Multidrug Efflux pump

emrD CTCAGCAGTATGGTGGTAAGCATT ACCAGGCGCCGAAGAAC Multidrug Efflux pump √ √

marR-01 GCGGCGTACTGGTGAAGCTA TGCCCTGGTCGTTGATGA Multidrug Efflux pump

mdetl1 ATACAGCAGTGGATATTGGTTTAATTGT TGCATAAGGTGAATGTTCCATGA Multidrug Efflux pump

UniProtKB Database

mdtA CCTAACGGGCGTGACTTCA TTCACCTGTTTCAAGGGTCAAA Multidrug Efflux pump

mdtE/yhiU CGTCGGCGCACTCGTT TCCAGACGTTGTACGGTAACCA Multidrug Efflux pump √ √

mepA ATCGGTCGCTCTTCGTTCAC ATAAATAGGATCGAGCTGCTGGAT Multidrug Efflux pump √ √

mexA AGGACAACGCTATGCAACGAA CCGGAAAGGGCCGAAAT Multidrug Efflux pump √ √

mexD TTGCCACTGGCTTTCATGAG CACTGCGGAGAACTGTCTGTAGA Multidrug Efflux pump √ √

mexF CCGCGAGAAGGCCAAGA TTGAGTTCGGCGGTGATGA Multidrug Efflux pump √ √

mtrC-01 GGACGGGAAGATGGTCCAA CGTAGCGTTCCGGTTCGAT Multidrug Efflux pump

mtrC-02 CGGAGTCCATCGACCATTTG ATCGTCGGCAAGGAGAATCA Multidrug Efflux pump

mtrD-02 GGTCGGCACGCTCTTGTC TGAAGAATTTGCGCACCACTAC Multidrug Efflux pump

mtrD-03 CCGCCAAGCCGATATAGACA GGCCGGGTTGCCAAA Multidrug Efflux pump

oprD ATGAAGTGGAGCGCCATTG GGCCACGGCGAACTGA Multidrug Efflux pump

√ Quale et al., 2006

oprJ ACGAGAGTGGCGTCGACAA AAGGCGATCTCGTTGAGGAA Multidrug Efflux pump √ √

qacA TGGCAATAGGAGCTATGGTGTTT AAGGTAACACTATTTTCGGTCCAAATC Multidrug Efflux pump √ √

qacA/qacB TTTAGGCAGCCTCGCTTCA CCGAATCCAAATAAAACCCAATAA Multidrug Efflux pump √ √

qacH-01 GTGGCAGCTATCGCTTGGAT CCAACGAACGCCCACAA Multidrug Efflux pump

qacH-02 CATCGTGCTTGTGGCAGCTA TGAACGCCCAGAAGTCTAGTTTT Multidrug Efflux pump

sdeB CACTACCGCTTCCGCACTTAA TGAAAAAACGGGAAAAGTCCAT Multidrug Efflux pump

Su et al. 2015

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tolC-01 GGCCGAGAACCTGATGCA AGACTTACGCAATTCCGGGTTA Multidrug Efflux pump √ √

tolC-02 CAGGCAGAGAACCTGATGCA CGCAATTCCGGGTTGCT Multidrug Efflux pump √ √

tolC-03 GCCAGGCAGAGAACCTGATG CGCAATTCCGGGTTGCT Multidrug Efflux pump √ √

ttgA ACGCCAATGCCAAACGATT GTCACGGCGCAGCTTGA Multidrug Efflux pump

Daniels & Ramos 2009

ttgB TCGCCCTGGATGTACACCTT ACCATTGCCGACATCAACAAC Multidrug Efflux pump

Daniels & Ramos 2009

yceE/mdtG-01 TGGCACAAAATATCTGGCAGTT TTGTGTGGCGATAAGAGCATTAG Multidrug Efflux pump √ √

yceE/mdtG-02 TTATCTGTTTTCTGCTCACCTTCTTTT GCGTGGTGACAAACAGGCTTA Multidrug Efflux pump √ √

yceL/mdtH-01 TCGGGATGGTGGGCAAT CGATAACCGAGCCGATGTAGA Multidrug Efflux pump √ √

yceL/mdtH-02 CGCGTGAAACCTTAAGTGCTT AGACGGCTAAACCCCATATAGCT Multidrug Efflux pump √ √

yceL/mdtH-03 CTGCCGTTAAATGGATGTATGC ACTCCAGCGGGCGATAGG Multidrug Efflux pump √ √

yidY/mdtL-01 GCAGTTGCATATCGCCTTCTC CTTCCCGGCAAACAGCAT Multidrug Efflux pump √ √

yidY/mdtL-02 TGCTGATCGGGATTCTGATTG CAGGCGCGACGAACATAAT Multidrug Efflux pump √ √

putitive multidrug AATTTTGCCGATTATTGCTGAAA GATTGTCATCATTCGTTTATCACCAA Multidrug Efflux pump

Zhu et al. 2013

qac CAATAATAACCGAAATAATAGGGACAAGTT AATAAGTGTTCCTAGTGTTGGCCATAG Multidrug Efflux pump

Zhu et al. 2013

qacEdelta1-01 TCGCAACATCCGCATTAAAA ATGGATTTCAGAACCAGAGAAAGAAA Multidrug Efflux pump

Wang et al. 2008

qacEdelta1-02 CCCCTTCCGCCGTTGT CGACCAGACTGCATAAGCAACA Multidrug Efflux pump

Wang et al. 2008

rarD-02 TGACGCATCGCGTGATCT AAATTTTCTGTGGCGTCTGAATC Multidrug Efflux pump

Su et al. 2015

mexE GGTCAGCACCGACAAGGTCTAC AGCTCGACGTACTTGAGGAACAC Multidrug Efflux pump √ √

pmrA TTTGCAGGTTTTGTTCCTAATGC GCAGAGCCTGATTTCTCCTTTG Multidrug Efflux pump √ √

bacA-01 CGGCTTCGTGACCTCGTT ACAATGCGATACCAGGCAAAT Others cellular protection √ √ Lamichhane-Khadka et al., 2008

bacA-02 TTCCACGACACGATTAAGTCATTG CGGCTCTTTCGGCTTCAG Others cellular protection √ √ Lamichhane-Khadka et al., 2008

fosB TCACTGTAACTAATGAAGCATTAGACCAT CCATCTGGATCTGTAAAGTAAAGAGATC Others Antibiotic deactivate √ √

fosX GATTAAGCCATATCACTTTAATTGTGAAAG TCTCCTTCCATAATGCAAATCCA Others Antibiotic deactivate √ √

nisB GGGAGAGTTGCCGATGTTGTA AGCCACTCGTTAAAGGGCAAT Others Other/Unknown

Ortega et al. 2015

nimE TGCGCCAAGATAGGGCATA GTCGTGAATTCGGCAGGTTTA Others Antibiotic deactivate

Leiros et al. 2004

speA GCAAGAGGTATTTGCTCAACAAGA CAGGGTCACCCTCATAAAGAAAA Others Other/Unknown

Su et al. 2015

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pncA GCAATCGAGGCGGTGTTC TTGCCGCAGCCAATTCA Others cellular protection

fabK TTTCAGCTCAGCACTTTGGTCAT AAGGCATCTTTTTCAGCCAGTTC Others Antibiotic deactivate

Heath et al. 2002

folA CGAGCAGTTCCTGCCAAAG CCCAGTCATCCGGTTCATAATC Others Antibiotic deactivate

√ Myllykallio et al., 2017

dfrA1 GGAATGGCCCTGATATTCCA AGTCTTGCGTCCAACCAACAG Others cellular protection √ √ Kadlec et al., 2011

dfrA12 CCTCTACCGAACCGTCACACA GCGACAGCGTTGAAACAACTAC Others cellular protection √ √ Kadlec et al., 2011

sul1 CAGCGCTATGCGCTCAAG ATCCCGCTGCGCTGAGT Sulfonamide cellular protection √ √

sul2 TCATCTGCCAAACTCGTCGTTA GTCAAAGAACGCCGCAATGT Sulfonamide cellular protection √ √

sulA/folP-01 CAGGCTCGTAAATTGATAGCAGAAG CTTTCCTTGCGAATCGCTTT Sulfonamide cellular protection

sulA/folP-03 CACGGCTTCGGCTCATGT TGCCATCCTGTGACTAGCTACGT Sulfonamide cellular protection

tet(34) CTTAGCGCAAACAGCAATCAGT CGGTGATACAGCGCGTAAACT Tetracycline Antibiotic deactivate, cellular protection2 √ √

tet(37) GAGAACGTTGAAAAGGTGGTGAA AACCAAGCCTGGATCAGTCTCA Tetracycline Antibiotic deactivate

tetR-02 CGCGATAGACGCCTTCGA TCCTGACAACGAGCCTCCTT Tetracycline Efflux pump, cellular protection1

tetR-03 CGCGATGGAGCAAAAGTACAT AGTGAAAAACCTTGTTGGCATAAAA Tetracycline Efflux pump, cellular protection1

tetX AAATTTGTTACCGACACGGAAGTT CATAGCTGAAAAAATCCAGGACAGTT Tetracycline Antibiotic deactivate √ √

tet(32) CCATTACTTCGGACAACGGTAGA CAATCTCTGTGAGGGCATTTAACA Tetracycline cellular protection √ √

tet(36)-01 AGAATACTCAGCAGAGGTCAGTTCCT TGGTAGGTCGATAACCCGAAAAT Tetracycline cellular protection √ √

tet(36)-02 TGCAGGAAAGACCTCCATTACAG CTTTGTCCACACTTCCACGTACTATG Tetracycline cellular protection √ √

tetM-01 CATCATAGACACGCCAGGACATAT CGCCATCTTTTGCAGAAATCA Tetracycline cellular protection √ √

tetM-02 TAATATTGGAGTTTTAGCTCATGTTGATG CCTCTCTGACGTTCTAAAAGCGTATTAT Tetracycline cellular protection √ √

tetO-01 ATGTGGATACTACAACGCATGAGATT TGCCTCCACATGATATTTTTCCT Tetracycline cellular protection √ √

tetPB-01 ACACCTGGACACGCTGATTTT ACCGTCTAGAACGCGGAATG Tetracycline cellular protection √ √

tetPB-02 TGATACACCTGGACACGCTGAT CGTCCAAAACGCGGAATG Tetracycline cellular protection √ √

tetPB-03 TGGGCGACAGTAGGCTTAGAA TGACCCTACTGAAACATTAGAAATATACCT Tetracycline cellular protection √ √

tetPB-04 AGTGGTGCAAATACTGAAAAAGTTGT TTTGTTCCTTCGTTTTGGACAGA Tetracycline cellular protection √ √

tetPB-05 CTGAAGTGGAGCGATCATTCC CCCTCAACGGCAGAAATAACTAA Tetracycline cellular protection √ √

tetQ CGCCTCAGAAGTAAGTTCATACACTAAG TCGTTCATGCGGATATTATCAGAAT Tetracycline cellular protection √ √

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tetS TTAAGGACAAACTTTCTGACGACATC TGTCTCCCATTGTTCTGGTTCA Tetracycline cellular protection √ √

tetT CCATATAGAGGTTCCACCAAATCC TGACCCTATTGGTAGTGGTTCTATTG Tetracycline cellular protection √ √

tet(35) ACCCCATGACGTACCTGTAGAGA CAACCCACACTGGCTACCAGTT Tetracycline Efflux pump

tetA-01 GCTGTTTGTTCTGCCGGAAA GGTTAAGTTCCTTGAACGCAAACT Tetracycline Efflux pump √ √

tetA-02 CTCACCAGCCTGACCTCGAT CACGTTGTTATAGAAGCCGCATAG Tetracycline Efflux pump √ √

tetB-01 AGTGCGCTTTGGATGCTGTA AGCCCCAGTAGCTCCTGTGA Tetracycline Efflux pump √ √

tetB-02 GCCCAGTGCTGTTGTTGTCAT TGAAAGCAAACGGCCTAAATACA Tetracycline Efflux pump √ √

tetC-01 CATATCGCAATACATGCGAAAAA AAAGCCGCGGTAAATAGCAA Tetracycline Efflux pump √ √

tetC-02 ACTGGTAAGGTAAACGCCATTGTC ATGCATAAACCAGCCATTGAGTAAG Tetracycline Efflux pump √ √

tetD-01 TGCCGCGTTTGATTACACA CACCAGTGATCCCGGAGATAA Tetracycline Efflux pump √ √

tetD-02 TGTCATCGCGCTGGTGATT CATCCGCTTCCGGGAGAT Tetracycline Efflux pump √ √

tetE TTGGCGCTGTATGCAATGAT CGACGACCTATGCGATCTGA Tetracycline Efflux pump √ √

tetG-01 TCAACCATTGCCGATTCGA TGGCCCGGCAATCATG Tetracycline Efflux pump √ √

tetG-02 CATCAGCGCCGGTCTTATG CCCCATGTAGCCGAACCA Tetracycline Efflux pump √ √

tetH TTTGGGTCATCTTACCAGCATTAA TTGCGCATTATCATCGACAGA Tetracycline Efflux pump √ √

tetJ GGGTGCCGCATTAGATTACCT TCGTCCAATGTAGAGCATCCATA Tetracycline Efflux pump √ √

tetK CAGCAGTCATTGGAAAATTATCTGATTATA CCTTGTACTAACCTACCAAAAATCAAAATA Tetracycline Efflux pump √ √

tetL-01 AGCCCGATTTATTCAAGGAATTG CAAATGCTTTCCCCCTGTTCT Tetracycline Efflux pump √ √

tetL-02 ATGGTTGTAGTTGCGCGCTATAT ATCGCTGGACCGACTCCTT Tetracycline Efflux pump √ √

tetPA AGTTGCAGATGTGTATAGTCGTAAACTATCTATT TGCTACAAGTACGAAAACAAAACTAGAA Tetracycline Efflux pump √ √

tetV GCGGGAACGACGATGTATATC CCGCTATCTCACGACCATGAT Tetracycline Efflux pump √ √

tetU-01 GTGGCAAAGCAACGGATTG TGCGGGCTTGCAAAACTATC Tetracycline Other/Unknown √

vanA AAAAGGCTCTGAAAACGCAGTTAT CGGCCGTTATCTTGTAAAAACAT Vancomycin cellular protection √ √

vanB-01 TTGTCGGCGAAGTGGATCA AGCCTTTTTCCGGCTCGTT Vancomycin cellular protection √ √

vanB-02 CCGGTCGAGGAACGAAATC TCCTCCTGCAAAAAAAGATCAAC Vancomycin cellular protection √ √

vanC-01 ACAGGGATTGGCTATGAACCAT TGACTGGCGATGATTTGACTATG Vancomycin cellular protection √ √

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vanC-03 AAATCAATACTATGCCGGGCTTT CCGACCGCTGCCATCA Vancomycin cellular protection √ √

vanG ATTTGAATTGGCAGGTATACAGGTTA TGATTTGTCTTTGTCCATACATAATGC Vancomycin cellular protection √ √

vanHB GAGGTTTCCGAGGCGACAA CTCTCGGCGGCAGTCGTAT Vancomycin cellular protection √ √

vanHD GTGGCCGATTATACCGTCATG CGCAGGTCATTCAGGCAAT Vancomycin cellular protection √ √

vanRA-01 CCCTTACTCCCACCGAGTTTT TTCGTCGCCCCATATCTCAT Vancomycin cellular protection √ √

vanRA-02 CCACTCCGGCCTTGTCATT GCTAACCACATTCCCCTTGTTTT Vancomycin cellular protection √ √

vanRB GCCCTGTCGGATGACGAA TTACATAGTCGTCTGCCTCTGCAT Vancomycin cellular protection √ √

vanRC TGCGGGAAAAACTGAACGA CCCCCCATACGGTTTTGATTA Vancomycin cellular protection √ √

vanRC4 AGTGCTTTGGCTTATCTCGAAAA TCCGGCAGCATCACATCTAA Vancomycin cellular protection √ √

vanRD TTATAATGGCAAGGATGCACTAAAGT CGTCTACATCCGGAAGCATGA Vancomycin cellular protection √ √

vanSA CGCGTCATGCTTTCAAAATTC TCCGCAGAAAGCTCAATTTGTT Vancomycin cellular protection √ √

vanSB GCGCGGCAAATGACAAC TTTGCCATTTTATTCGCACTGT Vancomycin cellular protection √ √

vanSC-02 GCCATCAGCGAGTCTGATGA CAGCTGGGATCGTTTTTCCTT Vancomycin cellular protection √ √

vanSE TGGCCGAAGAAGCAGGAA CAATAATACTCGTCAAAGGAGTTCTCA Vancomycin cellular protection √ √

vanTC-01 CACACGCATTTTTTCCCATCTAG CAGCCAACAGATCATCAAAACAA Vancomycin cellular protection

vanTC-02 ACAGTTGCCGCTGGTGAAG CGTGGCTGGTCGATCAAAA Vancomycin cellular protection

vanTE GTGGTGCCAAGGAAGTTGCT CGTAGCCACCGCAAAAAAAT Vancomycin cellular protection √ √

vanTG CGTGTAGCCGTTCCGTTCTT CGGCATTACAGGTATATCTGGAAA Vancomycin cellular protection √ √

vanWB CGGACAAAGATACCCCCTATAAAG AAATAGTAAATTGCTCATCTGGCACAT Vancomycin cellular protection √ √

vanWG ACATTTTCATTTTGGCAGCTTGTAC CCGCCATAAGAGCCTACAATCT Vancomycin cellular protection √ √

vanXA CGCTAAATATGCCACTTGGGATA TCAAAAGCGATTCAGCCAACT Vancomycin cellular protection √ √

vanXB AGGCACAAAATCGAAGATGCTT GGGTATGGCTCATCAATCAACTT Vancomycin cellular protection √ √

vanXD TAAACCGTGTTATGGGAACGAA GCGATAGCCGTCCCATAAGA Vancomycin cellular protection √ √

vanYB GGCTAAAGCGGAAGCAGAAA GATATCCACAGCAAGACCAAGCT Vancomycin cellular protection √ √

vanYD-01 AAGGCGATACCCTGACTGTCA ATTGCCGGACGGAAGCA Vancomycin cellular protection √ √

vanYD-02 CAAACGGAAGAGAGGTCACTTACA CGGACGGTAATAGGGACTGTTC Vancomycin cellular protection √ √

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vanC1 AGGCGATAGCGGGTATTGAA CAATCGTCAATTGCTCATTTCC Vancomycin cellular protection

Zhu et al. 2013

vanC2/vanC3 TTTGACTGTCGGTGCTTGTGA TCAATCGTTTCAGGCAATGG Vancomycin cellular protection

Zhu et al. 2013

cIntI-1(class1) GGCATCCAAGCAGCAAG AAGCAGACTTGACCTGA Integron Integron

intI-1(clinic) CGAACGAGTGGCGGAGGGTG TACCCGAGAGCTTGGCACCCA Integron Integron

Francia et al., 1999

tnpA-01 CATCATCGGACGGACAGAATT GTCGGAGATGTGGGTGTAGAAAGT Transposase Transposase

Liebert et al., 1999

tnpA-02 GGGCGGGTCGATTGAAA GTGGGCGGGATCTGCTT Transposase Transposase

tnpA-03 AATTGATGCGGACGGCTTAA TCACCAAACTGTTTATGGAGTCGTT Transposase Transposase

Grinsted et al., 1982

tnpA-04 CCGATCACGGAAAGCTCAAG GGCTCGCATGACTTCGAATC Transposase Transposase

tnpA-05 GCCGCACTGTCGATTTTTATC GCGGGATCTGCCACTTCTT Transposase Transposase

tnpA-07 GAAACCGATGCTACAATATCCAATTT CAGCACCGTTTGCAGTGTAAG Transposase Transposase

IS613 AGGTTCGGACTCAATGCAACA TTCAGCACATACCGCCTTGAT Transposase Transposase

Tp614 GGAAATCAACGGCATCCAGTT CATCCATGCGCTTTTGTCTCT Transposase Transposase

1 - For statistical analyses, we classified these ARGs as efflux pump mechanism; 2 - we classified this ARG as antibiotic deactivate mechanism. FCA -

fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol; MLSB - macrolide, lincosamide and streptogramin; Others - the ARGs conferring

resistance to other antibiotic classes, including bacitracin, fosfomycin, imipenem, lantibiotic, nitroimidazole, pyrazinamide, triclosan, trimethoprim and unknown.

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Explanation of total population, GDP and meat production used as anthropogenic factors in this study

Table S3 Total population, GDP and meat production data collected according to the administrative regions in every basin

Basin Total population × 104 person

GDP × 108 yuan

Meat production × 104 t

Basin area km2

Reference

Hubian R. 97.1 709.19 N/A 73.77 Fujian Provincial Bureau of Statistics, 2013

Bantou R. 60.7 369.26 0.488 275.79

Shidou R. 60.7 369.26 0.488 275.79

Tingxi R. 51.4 198.59 3.2737 657.59

Dongzhen R. 125.4 414.19 7.0852 2324

Poyang L. 4504 12948.88 333.91 166900 Jiangxi Provincial Bureau of Statistics, 2013

Longgan L. 170.45 257.91 10.81 4094.5 Hubei Provincial Bureau of Statistics, 2013; Anhui Provincial Bureau of Statistics, 2013; Susong County Bureau of Statistics, 2013

Taibai L. 151.43 313.1 14.74 2901.35 Hubei Provincial Bureau of Statistics, 2013

Liangzi L. 237.82 1116.93 28.77 5568.8 Hubei Provincial Bureau of Statistics, 2013

Shengjin L. 161.9 417.45 8.4 8271.7 Anhui Provincial Bureau of Statistics, 2013; Chizhou Municipal Bureau of Statistics, 2013

Nanyi L. 121 249.03 5.83 3725.8 Anhui Provincial Bureau of Statistics, 2013; Xuanzhou District Bureau of Statistics, 2013Langxi County Bureau of Statistics, 2013

Taihu L. 5471.95 50916.68 132 37417.4 Jiangsu Provincial Bureau of Statistics, 2013; Zhejiang Statistical Yearbook 2013; National Bureau of Statistics of China, 2013

Gucheng L. 41.91 365.27 1.67 802.8 Jiangsu Provincial Bureau of Statistics, 2013

Shijiu L. 107.58 583.9 3.46 2420 Jiangsu Provincial Bureau of Statistics, 2013; Anhui Provincial Bureau of Statistics, 2013

Hongze L. 540.59 2088.25 36.05 11151.1 Jiangsu Provincial Bureau of Statistics, 2013

Luoma L. 483.98 1669.26 60.46 7585 Jiangsu Provincial Bureau of Statistics, 2013

Weishan L. 2546.55 9530.13 223.31 33769.6 Jiangsu Provincial Bureau of Statistics, 2013; Shandong Provincial Bureau of Statistics, 2013

Dongping L. 684.24 3178.42 51.27 10007.2 Shandong Provincial Bureau of Statistics, 2013

Hengshui L. 438.93 1011.5 31.02 8815 Hebei Provincial Bureau of Statistics, 2013

Baiyangdian L. 1135.14 2720.9 55.2 22190 Hebei Provincial Bureau of Statistics, 2013

Yuehai L. 204.63 1140.83 5.1 9491 Yinchuan Municipal Bureau of Statistics, 2012

Shahu L. 74.16 409.21 2.02 5309.5 Shizuishan Municipal Bureau of Statistics, 2012 Xinhai L. 74.16 409.21 2.02 5309.5

Daihai L. 24.55 74.49 2.29 2494 Inner Mongolia Autonomous Region Bureau of Statistics, 2013 Hasuhai L. 35.98 213.14 2.57 2712

Donghaizi L. 12.29 51.31 0.92 4166.6

Wuliangsuhai L. 34.31 122.92 3.43 7476

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Basin Total population × 104 person

GDP × 108 yuan

Meat production × 104 t

Basin area km2

Reference

Quansanhaizi L. 29.48 98.49 4.15 2492.9

Shenglihaizi L. 29.48 98.49 4.15 2492.9

Bei’er L. 24.75 274.67 4.08 47926

Wulanpao L. 24.75 274.67 4.08 47926

Hulun L. 24.75 274.67 4.08 47926

Huhenuo’er L. 5.86 78.1 1.79 21192

Xinmiaopao L. 289.8 1605.4 36.1 22000 Songyuan Municipal Bureau of Statistics, 2013; Jiling Provincial Bureau of Statistics, 2013

Kulipao L. 289.8 1605.4 36.1 22000

Yueliangpao L. 200.02 615.4 11.4 25685 Baicheng Municipal Bureau of Statistics, 2013; Jiling Provincial Bureau of Statistics, 2013

Xinhuangpao L. 200.02 615.4 11.4 25685

Lamasipao L. 281.7 4000.5 33.8 22161 Daqing Municipal Bureau of Statistics, 2012

Amutapao L. 281.7 4000.5 33.8 22161

Qijiapao L. 281.7 4000.5 33.8 22161

Tianhu L. 281.7 4000.5 33.8 22161

Dongxintunnanpao L. 281.7 4000.5 33.8 22161

Notes:

1. The administrative regions for data collection and estimation of every basin

The catchment descriptors were mainly determined by the principle that if only minor part of an

administrative region is located in a basin, the data of this region wouldn’t be considered in data

collection and estimation for this basin, except that the main cities of this region are located in

the basin; if all or major part of an administrative region is located in a basin, the data of this

region were collected and estimated for this basin. The following are the detailed regions

considered ascovering areas of each basin.

Hubian R.: Huli district in Xiamen prefecture of Fujian province.

Bantou R.: Jimei district in Xiamen prefecture of Fujian province.

Shidou R.: Jimei district in Xiamen prefecture of Fujian province.

Tingxi R.: Tongan district in Xiamen prefecture of Fujian province.

Dongzhen R.: Chenxiang district and Xianyou county in Putian prefecture of Fujian province.

Poyang L.: Jiangxi province

Longgan L.: Huangmei county in Huanggang prefecture of Hubei province; Susong county in

Anqing prefecture of Anhui province.

Taibai L.: Wuxue county and Huangmei county in Huanggang prefecture of Hubei province.

Liangzi L.: Jiangxia district in Wuhan prefecture of Hubei province; Liangzihu district in Ezhou

prefecture of Hubei province; Xianan district in Xianning prefecture of Hubei province; Daye

county in Huangshi prefecture of Hubei province.

Shengjin L.: Chizhou prefecture of Anhui province.

Nanyi L.: Xuanzhou district and Langxi county in Xuancheng prefecture of Anhui province.

Taihu L.: Wuxi, Changzhou, Zhengjiang and Suzhou prefectures of Jiangsu province; Shanghai;

Huzhou and Jiaxin prefectures of Zhejiang province.

Gucheng L.: Gaochun district in Nanjing prefecture of Jiangsu province.

Shijiu L.: Lishui district in Nanjing prefecture of Jiangsu province;

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Hongze L.: Huaian prefecture excluding counties of Lianshui and Jinhu; Sihong and Siyang

counties in Suqian prefecture of Jiangsu province.

Luoma L.: Suqian prefecture excluding counties of Sihong, Siyang and Muyang; Xinyi, Pizhou

and Suining counties in Xuzhou prefecture of Jiangsu province.

Weishan L.: Xuzhou prefecture excluding counties of Xinyi, Pizhou and Suining; Jining,

Zaozhuang and Heze prefectures of Shandong province.

Dongping L.: Taian and Laiwu prefectures of Shandong province.

Hengshui L.: Hengshui prefecture of Hebei province.

Baiyangdian L.: Baoding prefecture of Hebei province.

Yuehai L.: Yingchuan prefecture of Ningxia Hui Autonomous Region.

Shahu L.: Shizuishan prefecture of Ningxia Hui Autonomous Region.

Xinhai L.: Shizuishan prefecture of Ningxia Hui Autonomous Region.

Daihai L.: Liangcheng county in Ulanqab prefecture of Inner Mongolia Autonomous Region.

Hasuhai L.: Tumote left banner in Hohhot prefecture of Inner Mongolia Autonomous Region.

Donghaizi L.: Dengkou county in Bayannaoer prefecture of Inner Mongolia Autonomous

Region

Wuliangsuhai L.: Wulate Front Banner in Bayannaoer prefecture of Inner Mongolia

Autonomous Region.

Quansanhaizi L.: Wuyuan county in Bayannaoer prefecture of Inner Mongolia Autonomous

Region.

Shenglihaizi L.: Wuyuan county in Bayannaoer prefecture of Inner Mongolia Autonomous

Region.

Bei’er L.: Xinbaerhu right banner, Xinbaerhu left banner and Manzhouli county in Hulunbuir

prefecture of Inner Mongolia Autonomous Region.

Wulanpao L.: Xinbaerhu right banner, Xinbaerhu left banner and Manzhouli county in

Hulunbuir prefecture of Inner Mongolia Autonomous Region.

Hulun L.: Xinbaerhu right banner, Xinbaerhu left banner and Manzhouli county in Hulunbuir

prefecture of Inner Mongolia Autonomous Region.

Huhenuo’er L.: Chenbaerhu Banner in Hulunbuir prefecture of Inner Mongolia Autonomous

Region.

Xinmiaopao L.: Songyuan prefecture of Jiling province.

Kulipao L.: Songyuan prefecture of Jiling province.

Yueliangpao L.: Baicheng prefecture of Jiling province.

Xinhuangpao L.: Baicheng prefecture of Jiling province.

Lamasipao L.: Daqing prefecture of Heilongjiang province.

Amutapao L.: Daqing prefecture of Heilongjiang province.

Qijiapao L.: Daqing prefecture of Heilongjiang province.

Tianhu L.: Daqing prefecture of Heilongjiang province.

Dongxintunnanpao L.: Daqing prefecture of Heilongjiang province.

2. General Description of indicators

2.1. All data of indicators for each basin are derived from statistical data of the administrative

regions where were mainly covered by each basin, if not, the mainpopulation or larger cities in

administrative regions should be distributed within thebasin.

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2.2. Administrative region population is estimated in according with the annual sample survey on

population changes.

2.3. Meat production is the sum of pork, beef, poultry, mutton, and rabbit meat productions.

2.4. All the administrative region area used in this study is according to the latest administrative

division.

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Explanation of municipal domestic sewage factor

Table S4 Municipal domestic sewage data estimated according to the administrative regions in every basin Basin Municipal domestic sewage × 106 t Reference

Hubian R. 38.78

China Environment Year Book Editorial Board, 2013

Bantou R. 24.24

Shidou R. 24.24

Tingxi R. 20.53

Dongzhen R. 50.09

Poyang L. 1331.00

Longgan L. 55.89

Taibai L. 51.96

Liangzi L. 81.61

Shengjin L. 50.56

Nanyi L. 37.79

Taihu L. 3131.82

Gucheng L. 19.15

Shijiu L. 39.65

Hongze L. 246.95

Luoma L. 221.09

Weishan L. 901.81

Dongping L. 208.49

Hengshui L. 110.21

Baiyangdian L. 285.03

Yuehai L. 70.85

Shahu L. 25.68

Xinhai L. 25.68

Daihai L. 6.78

Hasuhai L. 9.94

Donghaizi L. 3.40

Wuliangsuhai L. 9.48

Quansanhaizi L. 8.15

Shenglihaizi L. 8.15

Bei’er L. 6.84

Wulanpao L. 6.84

Hulun L. 6.84

Huhenuo’er L. 1.62

Xinmiaopao L. 78.61

Kulipao L. 78.61

Yueliangpao L. 54.26

Xinhuangpao L. 54.26

Lamasipao L. 76.56

Amutapao L. 76.56

Qijiapao L. 76.56

Tianhu L. 76.56

Dongxintunnanpao L. 76.56

Note:

Municipal domestic sewage effluent (S) is mainly estimated according to the following equation.

S = So × P/Po (1)

Where So, municipal domestic sewage effluent of province; P, population in the administrative

regions in Table S3; Po, population in the province in Table S2.

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Explanation of aquatic production, number of patient diagnosed and treated, number of residential patient factors

Table S5 Aquatic production, number of patient diagnosed and treated, number of residential patient data in 2012 Basin Aquatic

production × 104 t

No. of patients diagnosed and treated × 108 person-time

No. of residential patients × 106 person-time

Reference

Hubian R. 82.08 1.92 510.16

National Bureau of Statistics of China, 2013

Bantou R. 82.08 1.92 510.16

Shidou R. 82.08 1.92 510.16

Tingxi R. 82.08 1.92 510.16

Dongzhen R. 82.08 1.92 510.16

Poyang L. 237 1.9 657.87

Longgan L. 596.44 5.41 1573.73

Taibai L. 388.95 3.06 862.08

Liangzi L. 388.95 3.06 862.08

Shengjin L. 207.49 2.35 711.65

Nanyi L. 207.49 2.35 711.65

Taihu L. 470.25 11.24 1855.98

Gucheng L. 345.26 4.51 952.9

Shijiu L. 552.75 6.86 1664.55

Hongze L. 345.26 4.51 952.9

Luoma L. 345.26 4.51 952.9

Weishan L. 501.08 10.34 2350.38

Dongping L. 155.82 5.83 1397.48

Hengshui L. 52.85 3.68 869.6

Baiyangdian L. 52.85 3.68 869.6

Yuehai L. 12.35 0.31 82

Shahu L. 12.35 0.31 82

Xinhai L. 12.35 0.31 82

Daihai L. 13.16 0.93 258.63

Hasuhai L. 13.16 0.93 258.63

Donghaizi L. 13.16 0.93 258.63

Wuliangsuhai L. 13.16 0.93 258.63

Quansanhaizi L. 13.16 0.93 258.63

Shenglihaizi L. 13.16 0.93 258.63

Bei’er L. 13.16 0.93 258.63

Wulanpao L. 13.16 0.93 258.63

Hulun L. 13.16 0.93 258.63

Huhenuo’er L. 13.16 0.93 258.63

Xinmiaopao L. 18.21 0.97 302.45

Kulipao L. 18.21 0.97 302.45

Yueliangpao L. 18.21 0.97 302.45

Xinhuangpao L. 18.21 0.97 302.45

Lamasipao L. 45.28 1.15 420.09

Amutapao L. 45.28 1.15 420.09

Qijiapao L. 45.28 1.15 420.09

Tianhu L. 45.28 1.15 420.09

Dongxintunnanpao L. 45.28 1.15 420.09

Note:

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The data of aquatic production, number of patient diagnosed and treated and number of

residential patient refer to the corresponding values in the province where each basin is located.

Number of patient diagnosed and/or treated and number of residential patient are sourced from

China Statistical Yearbook 2013 (National Bureau of Statistics of China, 2013). Aquatic

production includes aquaculture and capture in freshwater, but the latter only accounts for a

small proportion of total production in most basins.

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Table S6 ARG groups in the south/central China compared with the north Chinese lakes/reservoirs (independent sample t-test)

Absolute abundance (P) Normalized abundance (P)

Aminoglycoside < 0.05 < 0.05

Beta-Lactamase > 0.05 > 0.05

FCA > 0.05 > 0.05

MLSB > 0.05 > 0.05

Multidrug > 0.05 < 0.05

Sulfonamide > 0.05 > 0.05

Tetracycline > 0.05 > 0.05

Vancomycin > 0.05 > 0.05

Others > 0.05 > 0.05

All ARGs > 0.05 < 0.01

FCA - fluoroquinolone, quinolone, florfenicol, chloramphenicol, and amphenicol; MLSB -

macrolide, lincosamide and streptogramin; Others - the ARGs conferring resistance to other

antibiotic classes, including bacitracin, fosfomycin, imipenem, lantibiotic, nitroimidazole,

pyrazinamide, triclosan, trimethoprim and unknown.

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Table S7 The richness and absolute abundance of ARGs that are unique and shared between the south/central and the north Chinese lakes/reservoirs

South/central unique shared North unique

Aminoglycoside richness 2 (8.7%) 20 (87.0%) 1 (4.3%)

abundance 3.45 × 104(0.11%) 3.07 × 107 (96.76%) 9.93 × 105 (3.13%)

Beta-Lactamase richness 4 (10.81%) 26 (70.27%) 7 (18.92%)

abundance 1.47 × 105 (0.15%) 9.83 × 107 (98.42%) 1.43 × 106 (1.43%)

FCA richness 0 (0.0%) 6 (100.0%) 0 (0.0%)

abundance 0 (0.00%) 2.88 × 106 (100.00%) 0 (0.00%)

MLSB richness 2 (8.0%) 17 (68.0%) 6 (24.0%)

abundance 5.60 × 104 (0.41%) 1.15 × 107 (84.47%) 2.05 × 106 (15.12%)

Multidrug richness 2 (5.56%) 30 (83.33%) 4 (11.11%)

abundance 4.21 × 104 (0.02%) 2.15 × 108 (99.84%) 3.07 × 105 (0.14%)

Sulfonamide richness 0 (0.0%) 2 (66.67%) 1 (33.33%)

abundance 0 (0.00%) 2.37 × 107 (99.96%) 9.62 × 103 (0.04%)

Tetracycline richness 2 (11.1%) 13 (72.2%) 3 (16.7%)

abundance 2.74 × 105 (1.43%) 1.90 × 107 (98.48%) 1.74 × 104 (0.09%)

Vancomycin richness 0 (0.0%) 8 (61.5%) 5 (38.5%)

abundance 0 (0.00%) 2.07 × 107 (99.12%) 1.83 × 105 (0.88%)

Others richness 0 (0.0%) 5 (83.33%) 1 (16.67%)

abundance 0 (0.00%) 6.17 × 106 (99.54%) 2.76 × 104 (0.45%)

All ARGs richness 12 (7.18%) 127 (76.05%) 28 (16.77%)

abundance 5.55 × 105 (0.13%) 4.27 × 108 (98.71%) 5.02 × 106 (1.16%)

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Table S8 Spearman’s correlations between ARGs, 16S rRNA gene and mobile genetic elements (MGEs) in China lakes/reservoirs (n = 42)

A

abundance

A

richness

16S

abundance

M

abundance

A abundance –

A richness 0.426** –

16S abundance 0.597** 0.113 –

M abundance 0.600** 0.403** 0.725** –

A - ARGs, 16S – 16S rRNA gene, M - mobile genetic elements. The abundance of ARGs and

MGEs is absolute abundance (copy number per litre water).

* P < 0.05, ** P < 0.01.

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Table S9 Spearman’s correlations between ARGs, 16S rRNA gene and MGEs in China lakes/reservoirs (n = 42)

A

abundance

A

richness

16S

abundance

M

abundance

A abundance –

A richness 0.412** –

16S abundance -0.467** 0.113 –

M abundance 0.299 0.444** -0.132 –

A - ARGs, 16S - 16S rRNA gene, M - mobile genetic elements (MGEs). The abundance of ARGs

and MGEs is normalized abundance (the ratio of ARGs and MGEs to 16S rRNA gene).

* P < 0.05, ** P < 0.01.

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Table S10 Spearman’s correlations between ARG groups and nine MGE marker genes (n = 42) cIntI-1 intI-1 tnpA-01 tnpA-02 tnpA-03 tnpA-04 tnpA-05 tnpA-07 Tp614

Aminoglycoside 0.01 0.31* 0.11 0.22 -0.05 0.68** 0.60** 0.25 0.07

Beta-Lactamase -0.26 0.39** 0.12 0.39** -0.09 0.27 0.32* 0.06 -0.01

FCA -0.22 0.16 0.31* 0.07 -0.08 0.40** 0.31* 0.25 -0.18

MLSB 0.03 0.39* 0.17 0.37* -0.24 0.43** 0.40** 0.17 -0.07

Multidrug 0.05 -0.01 0.20 0.18 0.09 0.49** 0.29 0.10 0.05

Others 0.12 -0.03 -0.04 0.07 -0.11 0.12 0.11 0.03 -0.04

Sulfonamide 0.18 0.04 0.31* 0.11 0.04 0.68** 0.35* 0.02 0.05

Tetracycline -0.08 0.29 0.15 0.38* -0.05 0.54** 0.31* 0.23 -0.03

Vancomycin -0.15 0.27 0.13 0.22 -0.20 0.50** 0.14 0.23 -0.16

The abundance of ARGs and MGEs is absolute abundance (copy number per litre water).

* P < 0.05, ** P < 0.01.

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Table S11 Spearman’s correlations between ARG groups and nine MGE marker genes (n = 42) cIntI-1 intI-1 tnpA-01 tnpA-02 tnpA-03 tnpA-04 tnpA-05 tnpA-07 Tp614

Aminoglycoside 0.11 0.02 -0.02 0.04 0.30 0.69** 0.60** 0.16 0.26

Beta-Lactamase -0.06 0.02 -0.11 0.22 0.24 0.36* 0.38* -0.14 0.05

FCA -0.03 0.13 0.16 0.02 0.19 0.46** 0.22 0.15 -0.09

MLSB 0.17 0.01 0.02 0.24 0.09 0.48** 0.29 0.07 0.12

Multidrug 0.12 -0.21 0.05 0.01 0.40** 0.53** 0.39* 0.01 0.20

Others 0.02 -0.20 -0.03 0.00 -0.01 -0.02 -0.07 -0.03 0.04

Sulfonamide 0.20 -0.12 0.16 -0.01 0.37* 0.70** 0.36* -0.11 0.21

Tetracycline 0.16 0.04 -0.10 0.11 0.33* 0.74** 0.49** -0.01 0.18

Vancomycin -0.18 0.05 0.04 0.10 0.00 0.47** 0.06 0.17 -0.00

The abundance of ARGs and MGEs is normalized abundance (the ratio of ARGs and MGEs to

16S rRNA gene).

* P < 0.05, ** P < 0.01.

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