Davies J E
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Ciba Found Symp. 1997;207:15-27; discussion 27-35.
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 gene 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 the processes are discussed. Are there prospects for drug intervention that eliminate or retard these natural evolutionary processes?
自20世纪40年代末抗生素问世以来，细菌病原体（及其亲缘种）中的抗生素抗性基因一直在无情地传播。这种生存现象最初被描述为改变药物靶点的点突变的出现，但在20世纪50年代中期，日本报道了可传播的抗生素抗性基因。从那时起，这两种抗性策略经常协同使用。对于某些类型的抗生素，仅发现了通过突变产生的抗性，而对于其他抗生素，仅发现了通过获得质粒产生的抗性。关于“抗生素前”时代细菌病原体中是否存在抗生素抗性，存在相互矛盾的证据；然而，抗生素抗性的进化可能发生在短时间内。因此，抗生素抗性基因在环境中必定普遍存在，但其来源仍有待最终确定。本文探讨了抗生素抗性基因起源于细菌群体的观点，这些基因要么是真正的抗性基因，要么是编码代谢功能的基因。此外，还讨论了不同遗传元件获得异源抗性决定子的情况、它们的属间交换机制以及抗生素在这些过程中可能发挥的作用。是否有可能通过药物干预来消除或延缓这些自然进化过程？
