Rifamycin antibiotics and the mechanisms of their failure

Rebekah A. Adams; Gabrielle Leon; Natalia M. Miller; Saira P. Reyes; Chantal H. Thantrong; Alina M. Thokkadam; Annabel S. Lemma; Darshan M. Sivaloganathan; Xuanqing Wan; Mark P. Brynildsen

doi:10.1038/s41429-021-00462-x

Rifamycin antibiotics and the mechanisms of their failure

Rebekah A. Adams, Gabrielle Leon, Natalia M. Miller, Saira P. Reyes, Chantal H. Thantrong, Alina M. Thokkadam, Annabel S. Lemma, Darshan M. Sivaloganathan, Xuanqing Wan, Mark P. Brynildsen

Research output: Contribution to journal › Review article › peer-review

31 Scopus citations

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.

Original language	English (US)
Pages (from-to)	786-798
Number of pages	13
Journal	Journal of Antibiotics
Volume	74
Issue number	11
DOIs	https://doi.org/10.1038/s41429-021-00462-x
State	Published - Nov 2021

All Science Journal Classification (ASJC) codes

Drug Discovery
Pharmacology

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title = "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.",

author = "Adams, {Rebekah A.} and Gabrielle Leon and Miller, {Natalia M.} and Reyes, {Saira P.} and Thantrong, {Chantal H.} and Thokkadam, {Alina M.} and Lemma, {Annabel S.} and Sivaloganathan, {Darshan M.} and Xuanqing Wan and Brynildsen, {Mark P.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to the Japan Antibiotics Research Association.",

year = "2021",

month = nov,

doi = "10.1038/s41429-021-00462-x",

language = "English (US)",

volume = "74",

pages = "786--798",

journal = "Journal of Antibiotics",

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AU - Adams, Rebekah A.

AU - Leon, Gabrielle

AU - Miller, Natalia M.

AU - Reyes, Saira P.

AU - Thantrong, Chantal H.

AU - Thokkadam, Alina M.

AU - Lemma, Annabel S.

AU - Sivaloganathan, Darshan M.

AU - Wan, Xuanqing

AU - Brynildsen, Mark P.

PY - 2021/11

Y1 - 2021/11

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AB - 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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Rifamycin antibiotics and the mechanisms of their failure

Abstract

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