6S RNA-dependent antibiotic susceptibility

Autor: Marick Esberard, Marc Hallier, Wenfeng Liu, Claire Morvan, Lionello Bossi, Nara Figueroa-Bossi, Brice Felden, Philippe Bouloc
Přispěvatelé: Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was supported by the Agence Nationale de la Recherche [ANR-19-CE12-0006-01 (RRARE)]. M.E. and W. L were the recipient of scholarships from the Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation (MESRI) and Chinese scholarship council (CSC), respectively., ANR-19-CE12-0006,RRARE,ARN Régulateurs et Résistance aux Antibiotiques(2019)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Popis: Bacterial small RNAs (sRNAs) contribute to a variety of regulatory mechanisms that modulate wide ranging 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 in Escherichia coli, S. aureus 6S RNA does not appear to play a critical role in the transition from exponential to stationary phase, but affects σB-regulated expression in prolonged stationary phase. Nevertheless, its protective effect against rifampicin is independent of alternative sigma factor σB activity. Our results suggest that 6S RNA helps maintain RNAP-σA integrity in S. aureus, which could in turn help bacteria withstand low concentrations of RNAP inhibitors.
Databáze: OpenAIRE