Université Montpellier 1, Centre d'Etudes d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), CNRS, UMR 5236, 4 Bd Henri IV, CS 69033, F-34965 Montpellier, Cedex 2, France.
Int J Antimicrob Agents. 2010 Jun;35(6):519-23. doi: 10.1016/j.ijantimicag.2009.12.017. Epub 2010 Feb 24.
The first antibiotic of the ansamycin family, rifampicin (RIF), was isolated in 1959 and was introduced into therapy in 1962; it is still a first-line agent in the treatment of diseases such as tuberculosis, leprosy and various biofilm-related infections. The antimicrobial activity of RIF is due to its inhibition of bacterial RNA polymerase (RNAP). Most frequently, bacteria become resistant to RIF through mutation of the target; however, this mechanism is not unique. Other mechanisms of resistance have been reported, such as duplication of the target, action of RNAP-binding proteins, modification of RIF and modification of cell permeability. We suggest that several of these alternative resistance strategies could reflect the ecological function of RIF, such as autoregulation and/or signalling to surrounding microorganisms. Very often, resistance mechanisms found in the clinic have an environmental origin. One may ask whether the introduction of the RIF analogues rifaximin, rifalazil, rifapentine and rifabutin in the therapeutic arsenal, together with the diversification of the pathologies treated by these molecules, will diversify the resistance mechanisms of human pathogens against ansamycins.
第一代安莎霉素类抗生素利福平（RIF）于 1959 年被分离出来，并于 1962 年引入临床治疗；它仍然是治疗结核病、麻风病和各种生物膜相关感染等疾病的一线药物。RIF 的抗菌活性是由于其抑制细菌 RNA 聚合酶（RNAP）。大多数情况下，细菌通过靶标突变对 RIF 产生耐药性；然而，这种机制并不是唯一的。已经报道了其他耐药机制，如靶标的复制、RNAP 结合蛋白的作用、RIF 的修饰和细胞通透性的修饰。我们认为，这些替代耐药策略中的几种可能反映了 RIF 的生态功能，如自我调节和/或向周围微生物发出信号。临床上发现的耐药机制通常具有环境起源。人们可能会问，随着 RIF 类似物利福昔明、利福喷丁、利福布汀在治疗中的引入，以及这些分子治疗的疾病多样化，是否会使人类病原体对安莎霉素类药物的耐药机制多样化。
