自然环境中的抗生素

1、Antibiotic Resistant Genes in Natural Environment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（Antibiotic Resistance Genes, 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 stated that “The analysis of bacterial isolates from pre-antibiotic era demonstrated that the copy number of different p

2、lasmids carried by pathogenic bacteria were essentially the same that can be found today”. The pre-antibiotic plasmids did not carry the antibiotic resistance genes, therefore the acquisition and further dissemination among pathogenic bacteria is the consequence of strong antibiotic selective pressu

3、re as a result of antibiotic therapy 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。The genetic modified organism needs to be carefully analyzed before they are introduced in the field as they may cause spread of antibiotic resistance genes in the population.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

4、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。Although there is a substantial concern over the potential effect of antibiotic resistance genes used for modifying organisms that can be released in the environment (20), the effect that changes to the environment may have on the population dynamics of bacte

5、ria and their antibiotic resistance genes has received much less attention (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。The study of transmission, intrinsic resistance to antibiotics and tendency to accumulate resistance genes are needed to under

6、stand the underlying mechanism 42. The study of antibiotic resistance in natural ecosystems is still underway. The most important question that is not yet answered is distribution of antibiotic resistance genes in nature.Antibiotics and Antibiotic Resistance Genes in Natural Environments对非临床环境中抗生素和抗

7、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。A better understanding of the ecological role for antibiotics and antibiotic resistance in nonclinical environments (Fig. 1) may eventually help to predict and counteract the emergence and future evolution of resistance (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

8、同。Antibiotic properties at therapeutic concentrations would also have distinct functions at the lower concentrations probably encountered in nature.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, molecules formerly classified as delivering signals for intermicrobial communication have subsequently been

9、found to possess demonstrable antibiotic activity (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。The huge number of antibiotic resistance genes found in the environment (8) raises the obvious question of why so many have evolved. Recent work has shown a pronounced bread

10、th of utilization of antibiotics as a source of nutrients by bacteria.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, it seems clear why antibiotic-producing microorganisms should possess determinants to help them resist the action of the antibiotics they produce, but

11、 it is less obvious why bacteria that do not themselves produce antibiotics should also possess multiple resistance determinants (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。MDR elements are involved in other processes such as detoxification of metabolic intermediates, virulence, and s

12、ignal trafficking.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, the dual nature of antibiotics as both signals and weapons can explain how genes can nevertheless contribute to the protection from antibiotic threat.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。In contrast, previously unrecognized antibiotic resi

13、stance genes that may emerge in the future already exist in many as yet ignored environmental organisms (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。Whether anthropogenic changes of the environment might enrich the population of resistant bacteria and facilitate the transfer of resistance genes to human p

14、athogens.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。Other types of contamination may also select for antibiotic resistance in nature. For instance, heavy metal pollution can select for antibiotic resistance (26), and stress conditions, as found in polluted en

15、vironments, have the potential to increase recombination and horizontal gene transfer in a way that favors the dissemination of antibiotic resistance genes (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。The presence of human commensal (and human-pathogenic) bacteria in the environment can be considered yet a

16、nother form of contamination.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。The increase in human population and the widespread lack of efficient wastewater treatment bring with them a risk of transfer of antibiotic resistance.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-driven increase in t

17、he concentrations of antibiotics in natural ecosystemsmay not only influence antibiotic resistance, but also affect the broader microbial population dynamics in different natural environments.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。The functional role these elements play in such environments is like

18、ly to be distinct from their“weapon/shield”function in clinical settings. In spite of the ecological relevance that antibiotics and resistance determinants have in nonclinical environments, there remains much to learn about the effect that human-driven changes of natural ecosystems may have on the e

19、volution and dissemination of resistance in nature. Yet, the relevance this is likely to have for the future of human health is clear.Application of real-time PCR array to the multiple detection of antibiotic resistant genes in glacier ice samplesGlacier environments harbor soil and enteric bacteria

20、. These bacteria may have been supplied at least in part from animals by means such as bird droppings, as well as local and global atmospheric circulation.自然环境中ARGs很多都是自然的抗生素产生菌，因此不因完全归因于医疗、兽医的活动，以及作物生产中的农药使用。In considering the nature and origin of antibiotic resistant genes, many of them are natura

21、lly harbored by antibiotic-producing organisms; it is not appropriate to regard that the detection of antibiotic resistant genes in the natural environment is totally attributable to medical and veterinary practices and the use of agrochemicals in crop production. Since the number of detected antibi

22、otic resistance genes was larger for Gulkana Glacier samples (8 genes) compared to rmqi Glacier (3 genes) and Rink Crags ice cap (0 gene), Gulkana Glacier in Alaska may be the glacier most affected by human industrial activities. Virtually no antibiotic resistant genes were detected from the Antarct

23、ic surface ice sample indicating that the “contamination” was still small compared to those in the glacier ice located in the northern hemisphere and not so separated from human industrial activities.Functional metagenomics reveals diverse b-lactamases in a remote Alaskan soilTo investigate antibiot

24、ic resistance genes among uncultured bacteria in an undisturbed soil environment, we undertook a functional metagenomic analysis of a remote Alaskan soil.Identifying sources of resistance genes and tracking their movement from unmanaged ecosystems to the human milieu will advance the effort to comba

25、t antibiotic resistance in human pathogens.The antibiotic resistome: the nexus of chemical and genetic diversityFigure 1 | The antibiotic resistome. The resistome comprises all of the antibiotic resistance genes. It includes resistance elements found in both pathogenic bacteria and antibiotic-produc

26、ing bacteria, and cryptic resistance genes (which are not necessarily expressed) that are present in bacterial chromosomes (genes that encode efflux proteins, -lactamases, antibiotic resistance of streptogramin). Resistance genes encode proteins that can either be highly specific to classes of antib

27、iotics or can be generalists with broad specificities. The resistome also includes precursor genes that encode proteins with modest antibiotic resistance activity, or affinity to antibiotics, that might evolve into effective resistance genes. Genes that encode resistance genes in antibiotic producer

28、s, or that are cryptic can be similar to the genes emerging in pathogenic bacteria; consequently these gene sets can significantly overlap.The role of antibiotics and antibiotic resistance in nature72Initially, on their introduction into clinical practice in the 1940s, antibiotics were extremely eff

29、icient in clearing pathogenic bacteria leading many to believe that infectious diseases would become a problem of the past and would be wiped out from all human populations eventually. However, the emergence and rapid dissemination of antibiotic-resistant pathogens, especially multi-drug-resistant b

30、acteria, during recent decades, exposed our lack of knowledge about the evolutionary and ecological processes taking place in microbial ecosystems.在20世纪40年代的临床实践中，抗生素是非常有效的，导致许多人认为，传染病将成为过去的问题，并最终将消灭所有的人类群体。然而，抗生素耐药的病原体，特别是多药耐药菌，在最近几十年中的出现和迅速传播，暴露我们的进化和生态过程发生在微生物生态系统的知识。It is now evident that microb

31、ial populations possess enormous metabolic diversity, from which they may deploy protective mechanisms allowing them to withstand the selective pressures imposed by their natural environment as well as human interventions such as antibiotics. Revealing the nature and functional role played by antibi

32、otics and antibiotic resistance in various natural ecosystems may help to understand the processes leading to the emergence of antibiotic-resistant pathogens. Finally, armed with knowledge accumulated through many years of genetic, genomic and metagenomic studies and with new concepts about antibiot

33、ics and antibiotic resistance, can we now predict the emergence and dissemination of resistance to newly introduced antibiotics?现在很明显，微生物种群拥有巨大的代谢多样性，他们可以部署保护机制，使他们能够承受的选择性压力所施加的自然环境，以及人为的干预措施，如抗生素。揭示抗生素和抗生素耐药性在各种自然生态系统中所扮演的性质和功能性作用，可能有助于了解导致抗生素耐药病原体出现的过程。最后，有多年的遗传知识积累的，基因组和基因研究和新的概念对抗生素和抗生素耐药性，我们现在

34、可以预测对引入新的抗生素的出现和传播性？Interestingly, the unknown evolutionary forces in apparently antibiotic-free environments may also contribute to the generation of novel diversity in antibiotic resistance genes (Allen et al., 2009). This metagenomic study of Alaskan soil not only uncovered a diverse and ancient

35、collection of -lactamase genes, but also revealed a novel gene encoding a bifunctional -lactamase that has never been encountered before.有趣的是，未知的进化力量，在明显的抗生素的环境中，也可能有助于产生新的多样性抗生素抗性基因（艾伦等人，2009）。这个宏基因组研究不仅发现了阿拉斯加土壤多样性和古集-内酰胺酶基因，而且还发现了一个新的基因编码的-内酰胺酶的双功能从未遇到过的In general, the history of antibiotic resistance genes can be divided into the macro- and microevolutionary periods, which can also be defined as the pre-antibiotic and antibiotic periods. The former is characterized by a long history of diversification in natural ecosystems, mos