Growth inhibition of Ureaplasma urealyticum by the proton pump inhibitor lansoprazole: direct attribution to inhibition by lansoprazole of urease activity and urea-induced ATP synthesis in U. urealyticum.
The proton pump inhibitors (PPIs) omeprazole and lansoprazole and the acid-activated analog of lansoprazole AG-2000, which potently inhibit the urease of Helicobacter pylori (K. Nagata, H. Satoh, T. Iwahi, T. Shimoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 1993), also inhibited the urease activities of cell-free extracts as well as intact cells of Ureaplasma urealyticum. The 50% inhibitory concentrations were between 1 and 25 microM. These compounds also inhibited the ATP synthesis induced by urea in ureaplasma cells. The 50% inhibitory concentrations for ATP synthesis were close to those for urease activity, but they were lower than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. In addition, one of the metabolites of lansoprazole found in human urine, M-VI, also inhibited ureaplasmal urease activity and the ATP synthesis induced by urea at almost the same concentrations as those of lansoprazole. The inhibition of PPIs against ureaplasma urease was very similar to those against H. pylori urease, suggesting that the inhibitory mechanism against these ureases was due to the blockage of the SH residues on the cysteine of the enzyme. Omeprazole, lansoprazole, AG-2000, and M-VI inhibited the growth of U. urealyticum. Since ureaplasma urease is thought to be involved in the pathogenicity of this organism in the urogenital tract, PPIs and their analogs may be useful as chemotherapeutic agents against diseases caused by U. urealyticum.
Nagata
K
K
Department of Bacteriology Hyogo College of Medicine, Japan.
Takagi
E
E
Satoh
H
H
Okamura
H
H
Tamura
T
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D064747:Lansoprazole; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D011725:Pyridines / Q000494:pharmacology; D014508:Urea / Q000494:pharmacology; D016990:Ureaplasma urealyticum / Q000187:drug effects* / Q000254:growth & development; D014510:Urease / Q000037:antagonists & inhibitors*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D011725:Pyridines; D064747:Lansoprazole; C058689:AG 2000; D000255:Adenosine Triphosphate; D014508:Urea; D014510:Urease; D009853:Omeprazole