自然环境中的抗生素

AntibioticResistantGenesinNaturalEnvironment前抗生素时代，致病菌所携带的质粒数量与现今的致病菌相同。但前抗生素时代，质粒并不携带抗生素抗性基因（AntibioticResistanceGenes,ARGs），因此致病菌对ARGs的获得及其传播/扩散是抗生素疗法选择压力的结果。Martinez[10]statedthat“Theanalysisofbacterialisolatesfrompre-antibioticerademonstratedthatthecopynumberofdifferentplasmidscarriedbypathogenicbacteriawereessentiallythesamethatcanbefoundtoday”.Thepre-antibioticplasmidsdidnotcarrytheantibioticresistancegenes,thereforetheacquisitionandfurtherdisseminationamongpathogenicbacteriaistheconsequenceofstrongantibioticselectivepressureasaresultofantibiotictherapy[10].遗传修饰的微生物在引进的过程中需要仔细地分析，因为它们可能会导致抗生素抗性基因在人群中的传播。Thegeneticmodifiedorganismneedstobecarefullyanalyzedbeforetheyareintroducedinthefieldastheymaycausespreadofantibioticresistancegenesinthepopulation.对于遗传修饰的微生物所携带的ARGs释放到环境中所带来的潜在影响，科学家极为担忧。因为这将造成环境中的细菌种群的动态变化。而对于这些抗生素抗性基因却关注甚微。Althoughthereisasubstantialconcernoverthepotentialeffectofantibioticresistancegenesusedformodifyingorganismsthatcanbereleasedintheenvironment(20),theeffectthatchangestotheenvironmentmayhaveonthepopulationdynamicsofbacteriaandtheirantibioticresistancegeneshasreceivedmuchlessattention(1).为了解抗生素潜在的机制，研究其传播、固有的抗性、以及积累抗性基因的倾向很有必要。自然生态系统中抗生素抗性的研究仍在进行中。对于ARGs在自然环境中的分布这一最为重要的问题仍然没有得到回答。Thestudyoftransmission,intrinsicresistancetoantibioticsandtendencytoaccumulateresistancegenesareneededtounderstandtheunderlyingmechanism[42].Thestudyofantibioticresistanceinnaturalecosystemsisstillunderway.Themostimportantquestionthatisnotyetansweredisdistributionofantibioticresistancegenesinnature.AntibioticsandAntibioticResistanceGenesinNaturalEnvironments对非临床环境中抗生素和抗生素耐药性的生态作用的深入研究有助于抵消抗性的出现、预测抗性未来演化。Abetterunderstandingoftheecologicalroleforantibioticsandantibioticresistanceinnonclinicalenvironments(Fig.1)mayeventuallyhelptopredictandcounteracttheemergenceandfutureevolutionofresistance(2).在治疗浓度的抗生素性质与自然环境中碰到的更低浓度的情况相比，其呈现出的功能有可能不同。Antibioticpropertiesattherapeuticconcentrationswouldalsohavedistinctfunctionsatthelowerconcentrationsprobablyencounteredinnature.曾经被认为是微生物间的信号传递分子，后来被发现具有明显的抗菌活性。Similarly,moleculesformerlyclassifiedasdeliveringsignalsforintermicrobialcommunicationhavesubsequentlybeenfoundtopossessdemonstrableantibioticactivity(5).自然环境中大量的ARGs的出现，引起了这样一个问题，为什么会有这么的ARGs被进化出来呢？进来的研究显示，抗生素可以被细菌当作营养物质而加以利用。Thehugenumberofantibioticresistancegenesfoundintheenvironment(8)raisestheobviousquestionofwhysomanyhaveevolved.Recentworkhasshownapronouncedbreadthofutilizationofantibioticsasasourceofnutrientsbybacteria.这就解释了为什么能产抗生素的微生物拥有决定因素，以帮助他们抵抗自己所产抗生素。但是，我们还是不明白，为什么不产抗生素的细菌，却具有多重耐药性。Equally,itseemsclearwhyantibiotic-producingmicroorganismsshouldpossessdeterminantstohelpthemresisttheactionoftheantibioticstheyproduce,butitislessobviouswhybacteriathatdonotthemselvesproduceantibioticsshouldalsopossessmultipleresistancedeterminants(10).Multi-drugresistance（MDR）也参与其它过程，如代谢中间体的解毒、毒力、以及信号交易。MDRelementsareinvolvedinotherprocessessuchasdetoxificationofmetabolicintermediates,virulence,andsignaltrafficking.因此，抗生素作为信号和武器的双重性质，有助于解释基因是如何在抗生素威胁中保护生物体的。Thus,thedualnatureofantibioticsasbothsignalsandweaponscanexplainhowgenescanneverthelesscontributetotheprotectionfromantibioticthreat.之前未被认识的ARGs，很可能早已存在于迄今为止被忽略的环境。Incontrast,previouslyunrecognizedantibioticresistancegenesthatmayemergeinthefuturealreadyexistinmanyasyetignoredenvironmentalorganisms(2).人为的环境变化，可能会丰富抗性细菌，并促进耐药基因转移到人类的病原体。Whetheranthropogenicchangesoftheenvironmentmightenrichthepopulationofresistantbacteriaandfacilitatethetransferofresistancegenestohumanpathogens.环境的污染也会对自然环境中抗生素抗性做出选择。如，重金属污染可以选择抗生素耐药性。在受污染的环境，压力条件有可能增加重组和水平基因转移，从而有利于抗生素抗性基因的传播。Othertypesofcontaminationmayalsoselectforantibioticresistanceinnature.Forinstance,heavymetalpollutioncanselectforantibioticresistance(26),andstressconditions,asfoundinpollutedenvironments,havethepotentialtoincreaserecombinationandhorizontalgenetransferinawaythatfavorsthedisseminationofantibioticresistancegenes(27).人类共生菌/人类致病菌在环境中的出现可以被认为是另一种形式的污染。Thepresenceofhumancommensal(andhuman-pathogenic)bacteriaintheenvironmentcanbeconsideredyetanotherformofcontamination.人口的增加和废水处理的非有效性会带来抗生素抗性转移这种危险的事情发生。Theincreaseinhumanpopulationandthewidespreadlackofefficientwastewatertreatmentbringwiththemariskoftransferofantibioticresistance.因人力驱动而引发的自然生态系统中抗生素浓度的增加，不仅会影响抗生素抗性，而且还会影响自然环境中微生物种群动态的扩大化。Human-drivenincreaseintheconcentrationsofantibioticsinnaturalecosystemsmaynotonlyinfluenceantibioticresistance,butalsoaffectthebroadermicrobialpopulationdynamicsindifferentnaturalenvironments.在这样的环境中，这些元素的功能与临床上所发挥的“武器/盾牌”的功能可能是不同的。Thefunctionalroletheseelementsplayinsuchenvironmentsislikelytobedistinctfromtheir“weapon/shield”functioninclinicalsettings.Inspiteoftheecologicalrelevancethatantibioticsandresistancedeterminantshaveinnonclinicalenvironments,thereremainsmuchtolearnabouttheeffectthathuman-drivenchangesofnaturalecosystemsmayhaveontheevolutionanddisseminationofresistanceinnature.Yet,therelevancethisislikelytohaveforthefutureofhumanhealthisclear.Applicationofreal-timePCRarraytothemultipledetectionofantibioticresistantgenesinglacierices