The impact of pollution on the evolution of antibiotic resistance in rhizobacteria

先前由作者资助的NERC研究证明了可能导致环境细菌抗生素耐药性水平增加的新机制，这种机制携带着高度移动的DNA元素，可以在细菌群体中迅速传播。选择压力是含有一组称为季铵化合物的工业污染。抗性基因的传播是通过水平基因转移发生的，这是一种非达尔文进化机制，因为它允许基因从一个细菌个体转移到另一个细菌个体，而不是亲本转移到后代。抗生素耐药基因从环境细菌转移到临床重要菌株被证明是一个日益严重的问题，尽管这一机制的全部潜力在很大程度上仍然未知。该提案旨在确定其他类型的污染物，特别是抗生素残留物和污水污泥中化学物质的复杂混合物，以及芳香烃是否可以产生抗生素耐药性的选择或允许其传播的移动元素，特别是一组临床上重要的抗生素，称为第三代头孢菌素（3gc）。这些抗生素是治疗中度至重度感染最常用的抗菌素之一。最近，在世界许多地区，广谱β -内酰胺酶的发病率急剧上升。特别需要调查广谱β -内酰胺酶和碳青霉烯酶的流行情况，它们被认为是最令人担忧的抗生素耐药基因之一，降低了一线临床重要药物的疗效。该项目旨在研究与植物根（根际）相关的土壤隔室是新出现的抗生素抗性基因的储存库的假设，以检测新的临床重要的β -内酰胺抗性基因和抗性机会主义病原体的存在。这些研究将在受污染和未受污染的地点进行，以研究人为污染对抗生素耐药性演变的贡献。研究将利用惠灵顿教授实验室开发的分子微生物生态学技能，以及临床微生物学方面的大量专业知识，特别是来自伯明翰大学和伯明翰心脏地带医院健康保护局的Hawkey教授的3GC抗性进化。这项研究将使我们能够评估与某些类型的污染物和土地管理措施（如污水污泥处置）有关的风险。此外，在环境储藏库中发现和鉴定新的耐药基因将为制药业提供早期预警，以帮助制定未来对抗耐药性的战略。

Previous NERC funded research by the authors demonstrated novel mechanisms which are likely to lead to increased levels of antibiotic resistance in environmental bacteria, carried on highly mobile DNA elements which can quickly spread through the bacterial population. The selective pressure was industrial pollution containing a group of compounds known as quaternary ammonium compounds. Spread of resistance genes occurs by horizontal gene transfer, a non-Darwinian mechanism of evolution, in that it allows transfer of genes from one individual bacterium to another rather than parent to offspring. Antibiotic resistance gene-transfer from environmental bacteria to clinically important strains is proving to be an increasing problem, although the full potential of this mechanism is still largely unknown. This proposal seeks to establish whether other types of pollutants, specifically antibiotic residues and complex mixtures of chemicals in sewage sludge, and aromatic hydrocarbons can produce selection for antibiotic resistance or the mobile elements which allow their dissemination, particularly a group of clinically important antibiotics known as third generation cephalosporins (3GCs). These antibiotics represent one of the most frequently prescribed antimicrobials for moderate to severe infections. Recently the incidence of extended spectrum beta-lactamases has risen steeply in many parts of the world. There is a particular need to investigate the prevalence of extended-spectrum beta-lactamases and carbapenemases which are considered to be amongst the most worrying antibiotic resistance genes, reducing the efficacy of frontline clinically important drugs. The project aims to investigate the hypothesis that the soil compartment associated with plant roots (rhizosphere) is a reservoir of emerging antibiotic resistance genes, to detect novel clinically significant beta-lactam resistance genes and the presence of resistant opportunist pathogens. These studies will be carried out in polluted and unpolluted sites to study the contribution of man made pollution to the evolution of antibiotic resistance. Research will utilise the molecular microbial ecology skills developed in Professor Wellington's lab together with the considerable expertise in clinical microbiology, specifically in the evolution of 3GC resistance of Professor Hawkey from the University of Birmingham and Health Protection Agency, Heartlands Hospital, Birmingham. The research will allow us to asses the risks associated with certain types of pollutants and land management practices such as sewage sludge disposal. In addition, discovery and characterisation of novel resistance genes in environmental reservoirs will provide early warning to the pharmaceutical industry to aid in the development of strategies to combat resistance in the future.