'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?
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Title'Happy the man, who, studying nature's laws, Thro' known effects can trace the secret cause.' Do we have enough pieces to solve the pyrazinamide puzzle?
Published inTijdschrift J Antimicrob Chemother 2018; advance online publication (ahead of print)
PubliekssamenvattingA low pH was assumed to be required for the activity of pyrazinoic acid (the active form of pyrazinamide) against Mycobacterium tuberculosis, but recently activity has been demonstrated at neutral pH. Renewed interest in pyrazinamide has led to an increasing number of potential targets and the suspicion that pyrazinamide is a 'dirty drug'. However, it is our opinion that the recent demonstration that pyrazinoic acid is active against PanD provides an alternative explanation for the secret of pyrazinamide's unusual activity. In this article we propose that PanD is the primary target of pyrazinoic acid but expression of pyrazinoic acid susceptibility requires an intact stress response. As the mycobacterial stress response requires the interaction of a number of genes, disruption of any could result in an inability to enter the susceptible phenotype. We believe this model can explain most of the recent observations of the seemingly diverse spectrum of activity of pyrazinamide.
- In Vivo-Selected Pyrazinoic Acid-Resistant Mycobacterium tuberculosis Strains Harbor Missense Mutations in the Aspartate Decarboxylase PanD and the Unfoldase ClpC1.
- Authors: Gopal P, Tasneen R, Yee M, Lanoix JP, Sarathy J, Rasic G, Li L, Dartois V, Nuermberger E, Dick T
- Issue date: 2017 Jul 14
- Pyrazinoic acid efflux rate in Mycobacterium tuberculosis is a better proxy of pyrazinamide resistance.
- Authors: Zimic M, Fuentes P, Gilman RH, Gutiérrez AH, Kirwan D, Sheen P
- Issue date: 2012 Jan
- Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid.
- Authors: Zhang Y, Wade MM, Scorpio A, Zhang H, Sun Z
- Issue date: 2003 Nov
- Pyrazinoic Acid Inhibits Mycobacterial Coenzyme A Biosynthesis by Binding to Aspartate Decarboxylase PanD.
- Authors: Gopal P, Nartey W, Ragunathan P, Sarathy J, Kaya F, Yee M, Setzer C, Manimekalai MSS, Dartois V, Grüber G, Dick T
- Issue date: 2017 Nov 10
- Iron enhances the antituberculous activity of pyrazinamide.
- Authors: Somoskovi A, Wade MM, Sun Z, Zhang Y
- Issue date: 2004 Feb