Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns.
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.
Tupin
Audrey
A
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. audrey.tupin@univ-montp1.fr
Gualtieri
Maxime
M
Roquet-Banères
Françoise
F
Morichaud
Zakia
Z
Brodolin
Konstantin
K
Leonetti
Jean-Paul
JP
D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D004463:Ecology; D005798:Genes, Bacterial; D006801:Humans; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*; D012641:Selection, Genetic
D000900:Anti-Bacterial Agents; D012293:Rifampin