title: Pyrazinoic acid decreases the proton motive force, respiratory ATP synthesis activity, and cellular ATP levels.
abstract: Pyrazinoic acid, the active form of the first-line antituberculosis drug pyrazinamide, decreased the proton motive force and respiratory ATP synthesis rates in subcellular mycobacterial membrane assays. Pyrazinoic acid also significantly lowered cellular ATP levels in Mycobacterium bovis BCG. These results indicate that the predominant mechanism of killing by this drug may operate by depletion of cellular ATP reserves.
authors.affiliation: Department of Molecular Cell Biology, Faculty of Earth and Life Sciences, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Anna C
authors.initials: AC
authors.lastname: Haagsma
authors.forename: Hoang
authors.initials: H
authors.lastname: Pham
authors.forename: Janneke J
authors.initials: JJ
authors.lastname: Maaskant
authors.forename: Selena
authors.initials: S
authors.lastname: Mol
authors.forename: Holger
authors.initials: H
authors.lastname: Lill
authors.forename: Dirk
authors.initials: D
authors.lastname: Bald
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis* / Q000378:metabolism; D000995:Antitubercular Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism*; D009163:Mycobacterium bovis / Q000187:drug effects / Q000378:metabolism; D018892:Proton-Motive Force / Q000187:drug effects*; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; C005296:pyrazinoic acid; D000255:Adenosine Triphosphate