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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.
S3
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.
S4
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.
S5
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.
S6
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.
S7
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).
S8
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.
S9
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 √ √
S10
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 √ √
S11
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 √ √
S12
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
S13
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 √ √
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
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
S16
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
S17
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 √ √
S18
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 √ √
S19
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 √ √
S20
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.
S21
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
S22
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;
S23
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.
S24
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.
S25
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.
S26
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:
S27
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.
S28
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.
S29
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%)
S30
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.
S31
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.
S32
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.
S33
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.
S34
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