Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Zhu, Jun-Hao; Wang, Bi-Wei; Pan, Miaomiao; Zeng, Yu-Na; Rego, Hesper; Javid, Babak
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 13
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06667-3
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract Metrics commonly used to describe antibiotic efficacy rely on measurements performed on bacterial populations. However, certain cells in a bacterial population can continue to grow and divide, even at antibiotic concentrations that kill the majority of cells, in a phenomenon known as antibiotic tolerance. Here, we describe a form of semi-heritable tolerance to the key anti-mycobacterial agent rifampicin, which is known to inhibit transcription by targeting the β subunit of the RNA polymerase (RpoB). We show that rifampicin exposure results inrpoB upregulation in a sub-population of cells, followed by growth. More specifically, rifampicin preferentially inhibits one of the tworpoB promoters (promoter I), allowing increasedrpoB expression from a second promoter (promoter II), and thus triggering growth. Disruption of promoter architecture leads to differences in rifampicin susceptibility of the population, confirming the contribution of rifampicin-inducedrpoB expression to tolerance. The antibiotic rifampicin inhibits transcription by targeting RpoB, a bacterial RNA polymerase subunit. Here, Zhu et al. show that certain cells in mycobacterial populations can continue to grow and divide in the presence of rifampicin due, paradoxically, to rifampicin-induced upregulation of therpoB gene.