Impact of the host environment on the antitubercular action of pyrazinamide

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Pyrazinamide remains the only drug in the tuberculosis pharmacopeia to drastically shorten first-line therapy from nine to six months. Due to its unparalleled ability to sterilize non-replicating bacilli and reduce relapse rates, PZA is expected to be irreplaceable in future therapies against tuberculosis. While the molecular target of PZA is unclear, recent pharmacokinetic studies using small animal models and patient samples have highlighted the importance of host metabolism and immune responses in PZA efficacy. Delineating which host factors are important for PZA action will be integral to the design of next-generation therapies to shorten current TB drug regimens as well as to overcome treatment limitations in some patients. In this review, we discuss evidence for influence of the host environment on PZA activity, targets for PZA mechanism of action, recent studies in PZA pharmacokinetics, PZA antagonism and synergy with other first-line anti-TB drugs, and implications for future research.

Original languageEnglish (US)
Pages (from-to)374-380
Number of pages7
JournalEBioMedicine
Volume49
DOIs
StatePublished - Nov 2019

Bibliographical note

Funding Information:
Research relevant for this review was supported by NIH grant R01 AI123146 to A.D.B. E.A.L was supported by a Postdoctoral Fellowship from the Ford Foundation of the National Academies of Science, Engineering, and Mathematics, U.S.A and the NIH diversity supplement award R01AI123146-03S1.

Funding Information:
Research relevant for this review was supported by NIH grant R01 AI123146 to A.D.B. E.A.L was supported by a Postdoctoral Fellowship from the Ford Foundation of the National Academies of Science, Engineering, and Mathematics , U.S.A and the NIH diversity supplement award R01AI123146-03S1 .

Publisher Copyright:
© 2019 The Author(s)

Keywords

  • Cell-mediated immunity
  • CoA biosynthesis
  • Granuloma
  • Pharmacokintetics
  • Pyrazinamide
  • Tuberculosis

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