Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns.

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Tupin A, Gualtieri M, Roquet-Baneres F, Morichaud Z, Brodolin K, Leonetti JP

Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns.

Int J Antimicrob Agents. 2010 Jun;35(6):519-23. doi: 10.1016/j.ijantimicag.2009.12.017. Epub 2010 Feb 24.

PubMed ID

20185278 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Rifampicin	DNA-directed RNA polymerase subunit beta	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details
Rifapentine	DNA-directed RNA polymerase subunit beta'	Protein	Mycobacterium tuberculosis	Yes	Inhibitor	Details