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6S RNA-Dependent Susceptibility to RNA Polymerase Inhibitors

Abstract : Bacterial small RNAs (sRNAs) contribute to a variety of regulatory mechanisms that modulate a wide range of pathways, including metabolism, virulence, and antibiotic resistance. We investigated the involvement of sRNAs in rifampicin resistance in the opportunistic pathogen Staphylococcus aureus. Using a competition assay with an sRNA mutant library, we identified 6S RNA as being required for protection against low concentrations of rifampicin, an RNA polymerase (RNAP) inhibitor. This effect applied to rifabutin and fidaxomicin, two other RNAP-targeting antibiotics. 6S RNA is highly conserved in bacteria, and its absence in two other major pathogens, Salmonella enterica and Clostridioides difficile, also impaired susceptibility to RNAP inhibitors. In S. aureus, 6S RNA is produced from an autonomous gene and accumulates in stationary phase. In contrast to what was reported for Escherichia coli, S. aureus 6S RNA does not appear to play a critical role in the transition from exponential to stationary phase but affects sigma(B)-regulated expression in prolonged stationary phase. Nevertheless, its protective effect against rifampicin is independent of alternative sigma factor sigma(B) activity. Our results suggest that 6S RNA helps maintain RNAP-sigma(A) integrity in S. aureus, which could in turn help bacteria withstand low concentrations of RNAP inhibitors.
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https://hal.archives-ouvertes.fr/hal-03658070
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Tuesday, May 3, 2022 - 3:15:38 PM
Last modification on : Friday, August 5, 2022 - 12:00:05 PM

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Marick Esberard, Marc Hallier, Wenfeng Liu, Claire Morvan, Lionello Bossi, et al.. 6S RNA-Dependent Susceptibility to RNA Polymerase Inhibitors. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2022, ⟨10.1128/aac.02435-21⟩. ⟨hal-03658070⟩

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