Origins, acquisition and dissemination of antibiotic resistance determinants

Since the introduction of antibiotics in the late 1940s there has been an inexorable propagation of antibiotic resistance genes in bacterial pathogens (and their relatives). This survival phenomenon was first characterized as the appearance of point mutations that altered drug targets, but in the mid-1950s transmissible antibiotic resistance genes were reported in Japan. Since this time both resistance strategies have been used, often in concert. For some types of antibiotic, only resistance by mutation has been identified, for others only resistance by plasmid acquisition. There is conflicting evidence with respect to the presence of antibiotic resistance in bacterial pathogens in the 'pre-antibiotic' era; however, it is likely that the evolution of antibiotic resistance occurred over short periods. Thus, antibiotic resistance genes must be common in the environment, but their derivation remains to be established conclusively. This paper examines the proposals that antibiotic resistance genes originated in the bacterial population, either as bona fide resistance genes or genes encoding metabolic functions. In addition, the acquisition of heterologous resistance determinants by different genetic elements, their intergeneric exchange mechanisms, and the possible roles of antibiotics in these processes are discussed. Are there prospects for drug intervention that eliminate or retard these natural evolutionary processes?