GROWTH-INHIBITION OF UREAPLASMA-UREALYTICUM BY THE PROTON PUMP INHIBITOR LANSOPRAZOLE - DIRECT ATTRIBUTION TO INHIBITION BY LANSOPRAZOLE OFUREASE 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. S himoyama, and T. Tamura, Antimicrob. Agents Chemother. 37:769-774, 199 3), also inhibited the urease activities of cell-free extracts as well as intact cells of Ureaplasma urealyticum. The 50% inhibitory concent rations were between 1 and 25 mu M. These compounds also inhibited the ATP synthesis induced by urea in ureaplasma cells. The 50% inhibitory concentrations for ATP synthesis mere close to those for urease activ ity, but they were lower than those of urease inhibitors, such as acet ohydroxamic acid, hydroxyurea, and thiourea, In addition, one of the m etabolites of lansoprazole found in human urine, M-VI, also inhibited ureaplasmal urease activity and the ATP synthesis induced by urea at a lmost 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 thes e ureases was due to the blockage of the SH residues on the cysteine o f the enzyme, Omeprazole, lansoprazole, AG-2000, and M-VI inhibited th e growth of U. urealyticum. Since ureaplasma urease is thought to be i nvolved in the pathogenicity of this organism in the urogenital tract, PPIs and their analogs may be useful as chemotherapeutic agents again st diseases caused by U. urealyticum.