01566nas a2200205   4500000000100000008004100001260001200042100001000054700001100064700001000075700001100085700001100096700001200107245011000119856008900229300000900318490000600327520101300333022001401346       2018                            d  c01/20181 aZhu J1 aWang B1 aPan M1 aZeng Y1 aRego H1 aJavid B00aRifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181997/pdf/41467_2018_Article_6667.pdf  a42180 v93 a<p>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 in rpoB upregulation in a sub-population of cells, followed by growth. More specifically, rifampicin preferentially inhibits one of the two rpoB promoters (promoter I), allowing increased rpoB 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-induced rpoB expression to tolerance.</p>  a2041-1723