Abstract
Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. Defining the mode of action for PZA will open new avenues for rational design of novel therapeutic approaches for the treatment of TB. In this review, we discuss the four prevailing models for PZA action, recent developments in modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.
| Original language | English (US) |
|---|---|
| Article number | e00070-19 |
| Journal | Microbiology and molecular biology reviews : MMBR |
| Volume | 84 |
| Issue number | 2 |
| DOIs | |
| State | Published - May 20 2020 |
Bibliographical note
Funding Information:This study 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. N.A.D. was supported by NIH institutional training grant T32 HL07741. All authors declare that they have no conflicts of interest.
Publisher Copyright:
© 2020 American Society for Microbiology. All Rights Reserved.
Keywords
- antimicrobial activity
- coenzyme A
- drug resistance
- drug resistance mechanisms
- drug susceptibility
- mode of action
- pyrazinamide
- tuberculosis
- Antimicrobial activity
- Drug resistance mechanisms
- Drug susceptibility
- Drug resistance
- Pyrazinamide
- Mode of action
- Tuberculosis
- Coenzyme A
PubMed: MeSH publication types
- Review
- Research Support, Non-U.S. Gov't
- Journal Article
- Research Support, N.I.H., Extramural
