Antibiotic Resistance in the Environment, with Particular Reference to MRSA

Publisher Summary

The evolution of antibiotic resistant bacteria is one of the most significant problems in modern medicine and poses a serious threat to human health. Increasingly the huge diversity of resistance genes that already exist in the environment is beginning to be appreciated. Understanding the selective pressures and mechanisms of gene transfer that drive dissemination of resistance genes not only in the clinic, but also in the wider environment is crucial for long-term strategies in the treatment of microbial disease. Modern farming practice is attempting to reduce dependency on antibiotics but this in itself may not reduce particular mechanisms of resistance such as genes carried on class 1 integrons, which is highlighted can be selected for by biocides in the environment. Understanding the ecology of resistance genes is extremely difficult as genes may be carried by unculturable bacteria (99.0–99.9% of bacteria). Movement of genes between environmental bacteria and the clinic has therefore been difficult to investigate in the past. However, modern molecular approaches such as epidemiological studies of key resistance determinants in total community DNA using quantitative real-time PCR allows detailed analyses and comparison of gene prevalence in the environment and human gut.

Introduction

The introduction of β‐lactam antibiotics (penicillins and cephalosporins) in the 1940s and 1950s probably represents the most important event in the battle against infection in human medicine. Even before widespread global use of penicillin, resistance was already recorded. E. coli producing a penicillinase was reported in Nature Journal in 1940 (Abraham and chain, 1940) and soon after a similar penicillinase was discovered in Staphylococcus aureus (Kirby, 1944). The appearance of these genes, so quickly after the discovery and before the widespread introduction of penicillin, clearly shows that the resistance genes pre‐dated the clinical use of the antibiotic itself.

Intuitive reasoning would suggest that antibiotic resistance occurs because of direct selection produced by the use of antibiotics in humans and animals. For example, the mutations associated with increased resistance to fluoroquinolones have been documented in specific regions of the gyrA, gyrB, grlA, and grlB genes, which are referred to as the quinolone resistance‐determining regions (QRDRs) (Piddock, 1998). Selection for resistance to a given antibiotic may take place within an infected human treated with antibiotics. However, selection may occur in other environments such as waste water treatment systems, agricultural environments where antibiotics may be of veterinary origin, or within an environmental background where antibiotic selection is provided by bacterial antibiotic producers.

In contrast to the scenario where resistance is conferred by mutation and selection by medical antibiotics, resistance can occur in an organism by the acquisition of a novel gene. New genes are acquired by horizontal gene transfer (HGT), through conjugation, transformation, or transduction. The origins of mobile antibiotic resistance genes may be from bacteria that have been subject to antibiotic selection in a nosocomial environment, or from environmental bacteria.

An example of an environment where HGT is likely to occur is soil. Practices such as sewage sludge and animal slurry application introduce complex mixtures of bacteria containing drug resistance genes, medical and veterinary antibiotics, and other chemicals such as detergents and surfactants to land, where interactions may occur with indigenous soil bacteria (Fig. 7.1).