RpoB

In a bacterium without the proper mutation(s) in rpoB rifampicin binds to a site near the fork in the β subunit and prevents the polymerase from transcribing more than two or three base pairs of any RNA sequence and stopping production of proteins within the cell. The majority of these mutations are located within an 81 base pair(bp) region in cluster I dubbed the "Rifampicin Resistance Determining Region (RRDR)". There are additional mutations which can occur in the β subunit of the polymerase which are located away from the rifampicin binding site that can also result in mild resistance. These mutations result in high rifampicin resistance with a relatively low loss of fitness. In addition to imparting resistance to rifampicin, certain rpoB mutations have been identified in 70% of Vancomycin Intermediate S. aureus (VISA) strains. == Physiological Effects of rpoB Mutations ==

The regions of the rpoB gene which are susceptible to mutations are typically well conserved, indicating they are important for life. This makes it very likely that mutations within these regions have some effect on the overall fitness of the organism. These physiological changes can include a reduced rate of growth, increased sensitivity to increases or decreases in temperature, and alterations to the properties of RNA chain elongation and transcription termination. Such changes are not universal across all bacteria, though. A mutation in codon 450 of M. tuberculosis leads to a minor loss of fitness, while the corresponding mutation in S. aureus results in bacteria barely able to survive. In Neisseria meningitidis rpoB mutations have been observed to increase expression of enzymes which are involved in metabolizing carbohydrates, as well as enzymes involved in the citric acid cycle and in transcription elongation. At the same time enzymes involved in ATP production, cell division, and lipid metabolism are all downregulated, or expressed at a lower than normal level. In M. tuberculosis mutations in the rpoB gene can significantly upregulate polyketide synthase, potentially indicating increased production of phthiocerol dimycocerosate, a lipid produced by M. tuberculosis and implicated in virulence of the bacteria. Mutations also impact promoter binding, elongation, termination, and transcription-coupled repair processes in the RNA polymerase itself. Because of this, rpoB mutations were used to study transcription mechanisms before interest shifted to their ability to impart antibiotic resistance. Particular mutations can even result in strains of M. tuberculosis which grow better in the presence of rifampicin than they do when the antibiotic is not present. In bacteria which are used to produce naturally occurring antibiotics such as erythromycin (Saccharopolyspora erythraea) and vancomycin (Amycolatopsis orientalis) certain rpoB mutations can increase the production of antibiotic by bacteria with those mutations. == References ==