title: Rifampicin-resistance, rpoB polymorphism and RNA polymerase genetic engineering.
abstract: Following its introduction in 1967, rifampicin has become a mainstay of therapy in the treatment of tuberculosis, leprosy and many other widespread diseases. Its potent antibacterial activity is due to specific inhibition of bacterial RNA polymerase. However, resistance to rifampicin was reported shortly after its introduction in the medical practice. Studies in the model organism Escherichia coli helped to define the molecular mechanism of rifampicin-resistance demonstrating that resistance is mostly due to chromosomal mutations in rpoB gene encoding the RNA polymerase β chain. These studies also revealed the amazing potential of the molecular genetics to elucidate the structure-function relationships in bacterial RNA polymerase. The scope of this paper is to illustrate how rifampicin-resistance has been recently exploited to better understand the regulatory mechanisms that control bacterial cell physiology and virulence, and how this information has been used to maneuver, on a global scale, gene expression in bacteria of industrial interest. In particular, we reviewed recent literature regarding: (i) the effects of rpoB mutations conferring rifampicin-resistance on transcription dynamics, bacterial fitness, physiology, metabolism and virulence; (ii) the occurrence in nature of "mutant-type" or duplicated rifampicin-resistant RNA polymerases; and (iii) the RNA polymerase genetic engineering method for strain improvement and drug discovery.
authors.affiliation: Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce 73100, Italy. Electronic address: pietro.alifano@unisalento.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Alifano
authors.affiliation: Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce 73100, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Palumbo
authors.affiliation: Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce 73100, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pasanisi
authors.affiliation: Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Lecce 73100, Italy.
authors.forename: Adelfia
authors.initials: A
authors.lastname: Talà
mesh_terms: D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics*; D055808:Drug Discovery; D024881:Drug Resistance, Bacterial; D005818:Genetic Engineering; D056084:Genetic Fitness; D008958:Models, Molecular; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit; D012293:Rifampin
keywords: Bacterial secondary metabolism; Bacterial virulence; Drug discovery; Rifampicin-resistance; Strain improvement