The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.
Role of Acid pH and Deficient Efflux of Pyrazinoic Acid in Unique Susceptibility of Mycobacterium tuberculosis to Pyrazinamide
Open accessAbstract
Pyrazinamide (PZA) is an important antituberculosis drug. Unlike most antibacterial agents, PZA, despite its remarkable in vivo activity, has no activity against Mycobacterium tuberculosis in vitro except at an acidic pH. M. tuberculosis is uniquely susceptible to PZA, but other mycobacteria as well as nonmycobacteria are intrinsically resistant. The role of acidic pH in PZA action and the basis for the unique PZA susceptibility of M. tuberculosis are unknown. We found that in M. tuberculosis , acidic pH enhanced the intracellular accumulation of pyrazinoic acid (POA), the active derivative of PZA, after conversion of PZA by pyrazinamidase. In contrast, at neutral or alkaline pH, POA was mainly found outside M. tuberculosis cells. PZA-resistant M. tuberculosis complex organisms did not convert PZA into POA. Unlike M. tuberculosis , intrinsically PZA-resistant M. smegmatis converted PZA into POA, but it did not accumulate POA even at an acidic pH, due to a very active POA efflux mechanism. We propose that a deficient POA efflux mechanism underlies the unique susceptibility of M. tuberculosis to PZA and that the natural PZA resistance of M. smegmatis is due to a highly active efflux pump. These findings may have implications with regard to the design of new antimycobacterial drugs.
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Antituberculosis drugs: Ten years of research
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The association between sterilizing activity and drug distribution into tuberculosis lesions
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THE MAGIC BULLETS AND TUBERCULOSIS DRUG TARGETS
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Metadata
- Authors
- Zhang, Y., Scorpio, A., Nikaido, H., & Sun, Z.
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 1999-04
- Volume
- 181
- Issue
- 7
- Pages
- 2044-2049
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- OpenAlex
- W2149808870
- Cited by
- 285
- References
- 21
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhang, Y., Scorpio, A., Nikaido, H., & Sun, Z. (1999). Role of Acid pH and Deficient Efflux of Pyrazinoic Acid in Unique Susceptibility of Mycobacterium tuberculosis to Pyrazinamide. Journal of Bacteriology. https://doi.org/10.1128/jb.181.7.2044-2049.1999
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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