Diverseandabundantantibioticresistancegenesi

See discussions, stats, and author profiles for this publication at: and abundant antibiotic resistancegenes in Chinese swine farmsArticle in Proceedings of the National Academy of Sciences · February 2013DOI: 10.1073/pnas.1222743110 · Source: PubMedCITATIONS273READS3328 authors, including:Some of the authors of this publication are also working on these related projects:Stroke View projectthe mechanism of organoarsenic synthesis View projectJian Qiang SuChinese Academy of Sciences83 PUBLICATIONS 1,330 CITATIONS SEE PROFILERobert D StedtfeldMichigan State University61 PUBLICATIONS 783 CITATIONS SEE PROFILESyed A HashshamMichigan State University128 PUBLICATIONS 2,375 CITATIONS SEE PROFILEJames M TiedjeMichigan State University770 PUBLICATIONS 61,546 CITATIONS SEE PROFILEAll content following this page was uploaded by Guang-Xia Guo on 21 January 2014.The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original documentand are linked to publications on ResearchGate, letting you access and read them immediately.DiverseandabundantantibioticresistancegenesinChineseswinefarmsYong-GuanZhua,b,1,2,TimothyA.Johnsonc,d,1,Jian-QiangSua,MinQiaob,Guang-XiaGuob,RobertD.Stedtfeldc,e,SyedA.Hashshamc,e,andJamesM.Tiedjec,d,2aKeyLabofUrbanEnvironmentandHealth,InstituteofUrbanEnvironment,ChineseAcademyofSciences,Xiamen361021,China;bResearchCenterforEco-EnvironmentalSciences,ChineseAcademyofSciences,Beijing100085,China;andcCenterforMicrobialEcology,DepartmentsofdPlant,SoilandMicrobialSciences,andeCivilandEnvironmentalEngineering,MichiganStateUniversity,EastLansing,MI48824ContributedbyJamesM.Tiedje,December31,2012(sentforreviewOctober31,2012)Antibioticresistancegenes(ARGs)areemergingcontaminantsposingapotentialworldwidehumanhealthrisk.IntensiveanimalhusbandryisbelievedtobeamajorcontributortotheincreasedenvironmentalburdenofARGs.DespitethevolumeofantibioticsusedinChina,littleinformationisavailableregardingthecor-respondingARGsassociatedwithanimalfarms.WeassessedtypeandconcentrationsofARGsatthreestagesofmanureprocessingtolanddisposalatthreelarge-scale(10,000animalsperyear)commer-cialswinefarmsinChina.In-feedortherapeuticantibioticsusedonthesefarmsincludeallmajorclassesofantibioticsexceptvancomy-cins.High-capacityquantitativePCRarraysdetected149uniqueresistancegenesamongallofthefarmsamples,thetop63ARGsbeingenriched192-fold(median)upto28,000-fold(maximum)comparedwiththeirrespectiveantibiotic-freemanureorsoilcon-trols.Antibioticsandheavymetalsusedasfeedsupplementswereelevatedinthemanures,suggestingthepotentialforcoselectionofresistancetraits.ThepotentialforhorizontaltransferofARGsbecauseoftransposon-specificARGsisimplicatedbytheenrichmentoftransposases—thetopsixallelesbeingenriched189-fold(median)upto90,000-foldinmanure—aswellasthehighcorrelation(r2=0.96)betweenARGandtransposaseabundance.Inaddition,abun-danceofARGscorrelateddirectlywithantibioticandmetalconcen-trations,indicatingtheirimportanceinselectionofresistancegenes.Diverse,abundant,andpotentiallymobileARGsinfarmsamplessuggestthatunmonitoreduseofantibioticsandmetalsiscausingtheemergenceandreleaseofARGstotheenvironment.concentratedanimalfeedingoperations|horizontalgenetransfer|growth-promotingantibiotics|tetracyclineThespreadandaggregationofantibiotic-resistantgenesintomultidrug-resistantpathogensischallenginglife-savinganti-biotictherapies(1,2).Indeed,theexpansionoftheantibioticresistancegenereservoirintheenvironmenthasbeencausedbyantibioticuseinhumansandanimals(3).Furthermore,agrow-ingbodyofdirectandindirectevidencefromthepast35y(4)establishesthatfarmantibioticusecorrelatesrepeatedlywiththeriseandspreadofassociatedresistancegenesinhumanpatho-gens,aswellasthedirecttransferofantibiotic-resistantbac-teriafromanimalstohumans(5–8).Antibioticusehasincreasedthefrequencyofhorizontalgenetransferandresistancegenefixationingenomes,leadingtothedevelopmentofdiversere-sistancegenesingenomicislands(9).Acinetobacterbaumanniiisacaseinpoint.In30y,itevolvedfrombeingcompletelyan-tibiotic-susceptibletobeingmultidrug-resistantbyexpandingagenomicislandby66kb,including45resistancegenes,whichwerehorizontallytransferredfromvariousgeneraofbacteria,someofwhichlikelyoriginatedfromtheenvironment(10).Antibiotic-resistantstrainscanthenbedistributedworldwide,aidedbyanumberofhumanfactors,butespeciallyinternationaltravelforcommerce,immigration,andrecreation(11).Antibi-oticresistancegenes(ARGs)arebecomingrecognizedasenvi-ronmentalpollutants,andactionisbeingsoughttopreservetheefficacyofantibiotics.TheWorldOrganizationforAnimalHealth,togetherwiththeUSFoodandDrugAdministrationandtheWorldHealthOrganization,urgeimprovedregulationofveterinaryantibioticuseinover100developingcountries(12).Chinaisthelargestantibioticsproducerandconsumerintheworld.Ina2007survey,theestimatedannualantibioticspro-ductioninChinawas210millionkg,and46.1%wereusedinlivestockindustries(13),atleastfourtimestheamo