01983nas a2200301   4500000000100000008004100001260001300042653002600055653001300081653002500094653003100119653001200150653002100162653001100183653001300194653002300207100001200230700001600242700002200258700001600280700001500296700001500311245009800326300001100424490000700435520122500442022001401667       2010                            d  c2010 Jun10aAnti-Bacterial Agents10aBacteria10aBacterial Infections10aDrug Resistance, Bacterial10aEcology10aGenes, Bacterial10aHumans10aRifampin10aSelection, Genetic1 aTupin A1 aGualtieri M1 aRoquet-Banères F1 aMorichaud Z1 aBrodolin K1 aLeonetti J00aResistance to rifampicin: at the crossroads between ecological, genomic and medical concerns.  a519-230 v353 a<p>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.</p>  a1872-7913