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Matches in SemOpenAlex for { <https://semopenalex.org/work/W4288458055> ?p ?o ?g. }

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• W4288458055 abstract "Rifampicin (RIF), the frontline drug against M. tuberculosis, is completely ineffective against M. abscessus, partially due to the presence of an ADP-ribosyltransferase (Arr) that inactivates RIF. Using RNA-seq, we show that exposure of M. abscessus to sublethal doses of RIF and Rifabutin (RBT), a close analog of RIF, results in an ∼25-fold upregulation of Mab_helR in laboratory and clinical isolates. An isogenic deletion in Mab_helR results in RIF/RBT hypersensitivity, and overexpression of Mab_helR confers RIF tolerance in M. tuberculosis. We demonstrate an increased HelR-RNAP association in RIF-exposed bacteria and a MabHelR-mediated dissociation of RNAP from stalled initiation complexes in vitro. Finally, we show that the tip of the PCh-loop of Mab_helR, present in proximity to RIF, is critical for conferring RIF resistance but dispensable for dissociation of stalled RNAP complexes, suggesting that HelR-mediated RIF resistance requires a step in addition to displacement of RIF-stalled RNAP." @default.
• W4288458055 created "2022-07-29" @default.
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• W4288458055 date "2022-09-01" @default.
• W4288458055 modified "2023-10-16" @default.
• W4288458055 title "Mycobacterium abscessus HelR interacts with RNA polymerase to confer intrinsic rifamycin resistance" @default.
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• W4288458055 doi "https://doi.org/10.1016/j.molcel.2022.06.034" @default.
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