2021
DOI: 10.1038/s41429-021-00462-x
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Rifamycin antibiotics and the mechanisms of their failure

Abstract: Rifamycins are a class of antibiotics that were first discovered in 1957 and are known for their use in treating tuberculosis (TB). Rifamycins exhibit bactericidal activity against many Gram-positive and Gram-negative bacteria by inhibiting RNA polymerase (RNAP); however, resistance is prevalent and the mechanisms range from primary target modification and antibiotic inactivation to cytoplasmic exclusion. Further, phenotypic resistance, in which only a subpopulation of bacteria grow in concentrations exceeding… Show more

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Cited by 39 publications
(39 citation statements)
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“…It is used in combination therapy (adjunctive with vancomycin) for the treatment of serious S. aureus infections such as endocarditis and BJI [ 27 ]. Rifampicin inhibits transcription via binding to the β-subunit of bacterial DNA-dependent RNA polymerase (encoded by rpoB gene), leading to suppression of RNA synthesis and subsequent cell death [ 219 , 220 ].…”
Section: Mrsa Resistance To Non-β-lactamsmentioning
confidence: 99%
“…It is used in combination therapy (adjunctive with vancomycin) for the treatment of serious S. aureus infections such as endocarditis and BJI [ 27 ]. Rifampicin inhibits transcription via binding to the β-subunit of bacterial DNA-dependent RNA polymerase (encoded by rpoB gene), leading to suppression of RNA synthesis and subsequent cell death [ 219 , 220 ].…”
Section: Mrsa Resistance To Non-β-lactamsmentioning
confidence: 99%
“…Rifamycin resistance is mainly associated with gram-positive bacteria. However, recent studies have reported that rifamycin resistance is highly prevalent in various bacterial groups [ 36 ]. Only one study has reported rifamycin resistance genes in Antarctic ecosystems with low anthropogenic impact [ 10 ].…”
Section: Discussionmentioning
confidence: 99%
“…Once the binding site is identified, a systematic medicinal chemistry campaign could lead to identification of inhibitors with higher potency and increased water solubility, a serious hurdle with SARS-CoV-2 RdRp (see Results). RIFs are particularly attractive lead molecules-they have been used as front-line drugs against tuberculosis for decades despite two shortcomings, accumulation of resistance mutations in the target rpoB gene and off-target effects in human cells [81]. To address these issues, hundreds of RIF derivatives have been synthesized [56,57] to increase their potency against bacterial RNAPs (including the common resistant mutants) while reducing unwanted side effects.…”
Section: Discussionmentioning
confidence: 99%