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

Abstract

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 M. 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.

Molecular characterization of thymidine kinase from Ureaplasma urealyticum: nucleoside analogues as potent inhibitors of mycoplasma growth

“…An exponential phase culture (10 7 cfu ml −1 ) was diluted with growth medium to different inoculum sizes. A total of 20 µl of this suspension was inoculated into 180 µl growth medium in 96 well tissue culture plates containing various amounts of nucleoside analogues (Nagata et al ., 1995). The plates were sealed and incubated aerobically for 24–72 h at 37°C.…”

“…The colour change was measured at 562 nm with a Titertek Multiscan spectrophotometer (Flow Laboratories) at different interval as described (Bloomster and Lynn, 1981). Mycoplasma pneumoniae growth was measured at various times, up to 7 days, by estimating the colour change in each well in comparison with the positive growth control of the same inoculum size (Nagata et al ., 1995). Relative growth was calculated by comparing with positive controls, which was set as 100%.…”

Molecular Biology and Pathogenicity of Mycoplasmas

“…Inhibition of the urease by flurofamide abolished both the chemical potential and the increase of ⌬p, such that ATP synthesis decreased to ϳ5% of the normally obtained levels (428). Lansoprazole, another specific urease inhibitor, also inhibited ATP synthesis and ureaplasma growth (320).…”

Complicated Urinary Tract Infection Is Associated with Uroepithelial Expression of Proinflammatory Protein S100A8

“…Although we did not assess urine pH at the time of collection, it is reasonable to assume that urine supersaturation with ammonia occurred in all animals with UTI since U. parvum uses urease to produce 95% of its ATP (16,24). Further, the organism could be located in the mucosal surface in all infected animals, thereby demonstrating ample opportunity for U. parvum to alter the ammonia concentration of the urine.…”