Antimicrobial resistance (AMR) is a global health threat requiring urgent attention and effective strategies for containment. AMR is fueled by wastewater mismanagement and global mobility, disseminating multidrug-resistant (MDR) strains worldwide. While global estimates of AMR burden have been informative, community-level understanding has received little attention despite reports of high AMR prevalence in healthy communities. We assessed the “invasion” of antibiotic resistance genes (ARGs) into the normal human flora by characterizing AMR Escherichia coli in local wastewaters contributed by a healthy youth population. This study estimated 26% (out of 300 isolates) resistant and 59% plasmid-bearing E. coli in local wastewater. Of the 78 AMR isolates, the frequency of mono-resistance was higher against tetracycline (32%), followed by kanamycin (17%) and chloramphenicol (9%). Five isolates were potentially MDR. We further sequenced four MDRs and four sensitive strains to comprehend the genome and resistome diversity in comparison to the global wastewater E. coli (genomes from the PATRIC database). The whole-genome analysis revealed extensive genome similarity among global isolates, suggesting global dissemination and colonization of E. coli. Global wastewater resistome majorly comprised ARGs against aminoglycosides (26%), beta-lactam (17%), sulfonamide (11%), and trimethoprim (8%). Resistance to colistin, a last-resort antibiotic, was prevalent in MDRs of European and South Asian isolates. A systems approach is required to address the AMR crisis on a global scale, reduce antibiotic usage, and increase the efficiency of wastewater management and disinfection.
Get full access to this article
View all access options for this article.
References
1.
MunkP, KnudsenBE, LukjancenkoO, et al.Abundance and diversity of the faecal resistome in slaughter pigs and broilers in nine European countries. Nat Microbiol, 2018; 3(8):898–908; doi: 10.1038/s41564-018-0192-9
Martinez JL. Short-sighted evolution of bacterial opportunistic pathogens with an environmental origin. Front Microbiol, 2014; 5:239; doi: 10.3389/fmicb.2014.00239
4.
Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 2022; 399(10325):629–655; doi: 10.1016/S0140-6736(21)02724-0
5.
VoigtAM, ZachariasN, TimmC, et al.Association between antibiotic residues, antibiotic resistant bacteria and antibiotic resistance genes in anthropogenic wastewater—An evaluation of clinical influences. Chemosphere, 2019; 241:125032; doi: 10.1016/j.chemosphere.2019.125032
6.
CheY, XiaY, LiuL, et al.Mobile antibiotic resistome in wastewater treatment plants revealed by nanopore metagenomic sequencing. Microbiome, 2019; 7(1):44; doi: 10.1186/s40168-019-0663-0
7.
Redondo-SalvoS, Fernandez-LopezR, RuizR, et al.Pathways for horizontal gene transfer in bacteria revealed by a global map of their plasmids. Nat Commun, 2020; 11(1):3602; doi: 10.1038/s41467-020-17278-2
8.
SchellenbergT, SubramanianV, GaneshanG, et al.Wastewater discharge standards in the evolving context of urban sustainability—The case of India. Front Environ Sci, 2020; 8; doi: 10.3389/fenvs.2020.00030
9.
AkibaM, SenbaH, OtagiriH, et al.Impact of wastewater from different sources on the prevalence of antimicrobial-resistant Escherichia coli in sewage treatment plants in South India. Ecotoxicol Environ Saf, 2015; 115:203–208; doi: 10.1016/j.ecoenv.2015.02.018
10.
ZhiS, BantingG, StothardP, et al.Evidence for the evolution, clonal expansion and global dissemination of water treatment-resistant naturalized strains of Escherichia coli in wastewater. Water Res, 2019; 156:208–222; doi: 10.1016/j.watres.2019.03.024
11.
HaenniM, DagotC, ChesneauO, et al.Environmental contamination in a high-income country (France) by antibiotics, antibiotic-resistant bacteria, and antibiotic resistance genes: Status and possible causes. Environ Int, 2022; 159:107047; doi: 10.1016/j.envint.2021.107047
12.
de KrakerMEA, StewardsonAJ, HarbarthS. Will 10 million people die a year due to antimicrobial resistance by 2050?. PLoS Med, 2016; 13(11):e1002184; doi: 10.1371/journal.pmed.1002184
13.
Davidova-GerzovaL, LausovaJ, SukkarI, et al.Hospital and community wastewater as a source of multidrug-resistant ESBL-producing. Escherichia coli. 2023; 13:1184081; doi: 10.3389/fcimb.2023.1184081
14.
MaratheNP, ReginaVR, WalujkarSA, et al.A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multidrug resistant integron-bearing bacteria. PLoS One, 2013; 8(10):e77310; doi: 10.1371/journal.pone.0077310
15.
LobovaTI, FeilEJ, PopovaLY. Multiple antibiotic resistance of heterotrophic bacteria isolated from Siberian lakes subjected to differing degrees of anthropogenic impact. Microb Drug Resist, 2011; 17(4):583–591; doi: 10.1089/mdr.2011.0044
BankevichA, NurkS, AntipovD, et al.SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol, 2012; 19(5):455–477; doi: 10.1089/cmb.2012.0021
18.
AntonopoulosDA, AssafR, AzizRK, et al.PATRIC as a unique resource for studying antimicrobial resistance. Brief Bioinform, 2019; 20(4):1094–1102; doi: 10.1093/bib/bbx083
19.
SimsGE, KimS-H.Whole-genome phylogeny of Escherichia coli/Shigella group by feature frequency profiles (FFPs). Proc Natl Acad Sci U S A, 2011; 108(20):8329–8334; doi: 10.1073/pnas.1105168108
20.
KaasRS, LeekitcharoenphonP, AarestrupFM, et al.Solving the problem of comparing whole bacterial genomes across different sequencing platforms. PLoS One, 2014; 9(8):e104984; doi: 10.1371/journal.pone.0104984
21.
LetunicI, BorkP. Interactive Tree Of Life (iTOL) v4: Recent updates and new developments. Nucleic Acids Res, 2019; 47(W1):W256–W259; doi: 10.1093/nar/gkz239
22.
BeghainJ, Bridier-NahmiasA, Le NagardH, et al.ClermonTyping: An easy-to-use and accurate in-silico method for Escherichia genus strain phylotyping. Microb Genom, 2018; 4(7):e000192; doi: 10.1099/mgen.0.000192
BessonovK, LaingC, RobertsonJ, et al.ECTyper: In silico Escherichia coli serotype and species prediction from raw and assembled whole-genome sequence data. Microb Genom, 2021; 7(12):000728; doi: 10.1099/mgen.0.000728
25.
LarsenMV, CosentinoS, RasmussenS, et al.Multilocus sequence typing of total-genome-sequenced bacteria. J Clin Microbiol, 2012; 50(4):1355–1361; doi: 10.1128/JCM.06094-11
26.
PageAJ, CumminsCA, HuntM, et al.Roary: Rapid large-scale prokaryote pan genome analysis. Bioinformatics, 2015; 31(22):3691–3693; doi: 10.1093/bioinformatics/btv421
27.
ZankariE, HasmanH, CosentinoS, et al.Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother, 2012; 67(11):2640–2644; doi: 10.1093/jac/dks261
28.
JoensenKG, ScheutzF, LundO, et al.Real-time whole-genome sequencing for routine typing, surveillance, and outbreak detection of verotoxigenic Escherichia coli. J Clin Microbiol, 2014; 52(5):1501–1510; doi: 10.1128/jcm.03617-13
29.
PetkauA, Stuart-EdwardsM, StothardP, et al.Interactive microbial genome visualization with GView. Bioinformatics, 2010; 26(24):3125–3126; doi: 10.1093/bioinformatics/btq588
30.
ShawLP, ChauKK, KavanaghJ, et al.Niche and local geography shape the pangenome of wastewater- and livestock-associated Enterobacteriaceae. Sci Adv, 2021; 7(15):eabe3868; doi: 10.1126/sciadv.abe3868
NjiE, KazibweJ, HambridgeT, et al.High prevalence of antibiotic resistance in commensal Escherichia coli from healthy human sources in community settings. Sci Rep, 2021; 11(1):3372; doi: 10.1038/s41598-021-82693-4
33.
TanejaN, SharmaM. Antimicrobial resistance in the environment: The Indian scenario. Indian J Med Res, 2019; 149(2):119–128; doi: 10.4103/ijmr.IJMR_331_18
34.
SeguniNZ, KimeraZI, MsafiriF, et al.Multidrug-resistant Escherichia coli and Klebsiella pneumoniae isolated from hospital sewage flowing through community sewage system and discharging into the Indian Ocean. Bull Natl Res Centre, 2023; 47(1):66; doi: 10.1186/s42269-023-01039-4
35.
OrlekA, AnjumMF, MatherAE, et al.Factors associated with plasmid antibiotic resistance gene carriage revealed using large-scale multivariable analysis. Sci Rep, 2023; 13(1):2500; doi: 10.1038/s41598-023-29530-y
36.
MengM, LiY, YaoH. Plasmid-mediated transfer of antibiotic resistance genes in soil. Antibiotics, 2022; 11(4):525; doi: 10.3390/antibiotics11040525
37.
KrauseKM, SerioAW, KaneTR, et al.Aminoglycosides: An overview. Cold Spring Harb Perspect Med, 2016; 6(6):a027029; doi: 10.1101/cshperspect.a027029
38.
Canadian Council of Ministers of the Environment (CCME). Canada-Wide Strategy for the Management of Municipal Wastewater Effluent—2014 Progress Report. Council of Ministers of the Environment: Whitehorse; February 17, 2009.
39.
QuJ, HuangY, LvX. Crisis of antimicrobial resistance in China: Now and the future. Front Microbiol, 2019; 10:2240; doi: 10.3389/fmicb.2019.02240
40.
ParnanenKMM, Narciso-da-RochaC, KneisD, et al.Antibiotic resistance in European wastewater treatment plants mirrors the pattern of clinical antibiotic resistance prevalence. Sci Adv, 2019; 5(3):eaau9124; doi: 10.1126/sciadv.aau9124
41.
MehdiY, Létourneau-MontminyM-P, GaucherM-L, et al.Use of antibiotics in broiler production: Global impacts and alternatives. Anim Nutr, 2018; 4(2):170–178; doi: 10.1016/j.aninu.2018.03.002
42.
JainP, BepariAK, SenPK, et al.High prevalence of multiple antibiotic resistance in clinical E. coli isolates from Bangladesh and prediction of molecular resistance determinants using WGS of an XDR isolate. Sci Rep, 2021; 11(1):22859; doi: 10.1038/s41598-021-02251-w
43.
TangdenT. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria. Ups J Med Sci, 2014; 119(2):149–153; doi: 10.3109/03009734.2014.899279
44.
ChiangYN, PenadesJR, ChenJ. Genetic transduction by phages and chromosomal islands: The new and noncanoni-cal. PLoS Pathog, 2019; 15(8):e1007878; doi: 10.1371/journal.ppat.1007878
45.
AnR, QiY, ZhangX-X, et al.Xenogenetic evolutionary of integrons promotes the environmental pollution of antibiotic resistance genes—Challenges, progress and prospects. Water Res, 2023; 231:119629; doi: 10.1016/j.watres.2023.119629
46.
JoddhaHB, MathakiyaRA, JoshiKV, et al.Profiling of antimicrobial resistance genes and integron from Escherichia coli isolates using whole genome sequencing. Genes, 2023; 14(6):1212.
47.
BabakhaniS, OloomiM. Transposons: The agents of antibiotic resistance in bacteria. J Basic Microbiol, 2018; 58(11):905–917; doi: 10.1002/jobm.201800204
48.
MulchandaniR, WangY, GilbertM, et al.Global trends in antimicrobial use in food-producing animals: 2020 to 2030. PLOS Glob Public Health, 2023; 3(2):e0001305; doi: 10.1371/journal.pgph.0001305
49.
KimM, ParkJ, KangM, et al.Gain and loss of antibiotic resistant genes in multidrug resistant bacteria: One Health perspective. J Microbiol, 2021; 59(6):535–545; doi: 10.1007/s12275-021-1085-9
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
