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

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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.