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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 their minimum inhibitory concentration, and tolerance, which is characterized by reduced rates of bacterial cell death, have been identified as additional causes of rifamycin failure. Here we summarize current understanding and recent developments regarding this critical antibiotic class.

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Acknowledgements

This work was supported by the 250th Anniversary Fund for Innovation in Undergraduate Education, the Program for Community Engaged Scholarship, and the Council on Science and Technology at Princeton University (MPB). This content is solely the responsibility of the authors and does not necessarily represent the views of the funding agencies.

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RAA, GL, NMM, SPR, CHT, AMT, ASL, DMS, XW, and MPB wrote and revised the paper.

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Correspondence to Mark P. Brynildsen.

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Adams, R.A., Leon, G., Miller, N.M. et al. Rifamycin antibiotics and the mechanisms of their failure. J Antibiot (2021). https://doi.org/10.1038/s41429-021-00462-x

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