Journal of Bacteriology & Parasitology

Novel urease inhibitors for the control of ureolytic microbial pathogens

3^rd International Congress on Bacteriology and Infectious Diseases

August 04-06, 2015 Valencia, Spain

Agnieszka Grabowiecka

Scientific Tracks Abstracts: J Bacteriol Parasitol

Abstract:

Ureolytic activity of bacterial pathogens is a main causative factor of severe clinical conditions concerning the human
gastric and urinary tract. The damaging effect to host organism results from alkalization of pathogens environment due to
ammonia release from urea molecules. The growing bacterial resistance to antimicrobial agents has stimulated studies on urease
inhibition as a way to control colonization with Helicobacter pylori and Proteus mirabilis. Within research of our Bioorganic
Chemistry Group a new class of urease inhibitors was proposed using available enzyme crystal structures. Investigated
aminophosphonates and aminophosphinates are extended transition state analogs of urease reaction. Their inhibition potency
against urease purified from H. pylori and Proteus mirabilis as well as assayed in whole-cell system exceeds clinically approved
acetohydroxamate (dissociation constants within micro molar range). Novel inhibitors were verified as agents for maintaining
ionic balance and preventing Proteus-induced struvite precipitation in artificial urine. In the presence of the studied
compounds maximum urine pH was 7.3 compared to 9.4 in untreated cultures. Precipitate formation was significantly reduced
as shown in 31P-NMR analysis. In microscopic examinations only single coffin-like crystals characteristic of early struvite
formation were present. In H. pylori reference strains repressed ureolysis reduced ability to survive incubations under strongly
acidic conditions. Besides urease inhibition, several structures bearing long aliphatic chains (C5, C6) additionally exhibited
moderate bacteriostatic effect. Minimal Inhibitory Concentrations were estimated using broth micro dilution method and
metabolic activity assay using tetrazolium salts (MTT). Reduced viability in the presence of urease inhibitors was validated by
fluorescence staining using LIVE/DEAD BacLight Kit by Molecular Probes.

Biography :

Agnieszka Grabowiecka currently working at Department of Bioorganic Chemistry, Wroclaw University of Technology, Poland.