Urease Inhibition: Alternative to Antimicrobial Treatment

Abstract

Bacteria induce disease by a number of mechanisms, e.g., production of toxins, enzymes, or antigens and/or resistance to phagocytosis. Braude (1) and Siemienski have suggested that Proteus species are pathogenic primarily because of their ability to synthesize the enzyme, urease. They suggested that urease-induced hydrolysis of urea in urine is the primary mediator of pathogenicity. This hypothesis is suported by clinical observations: 1) Proteus is infrequently implicated as a pathogen outside the urinary tract where urea concentrations are low; 2) Proteus is a major pathogen within the urinary tract; and 3) strains of Proteus that do not produce urease are relatively nonpathogenic. Experimental support of the hypothesis has also been provided by other investigators (2–5). Acetohydroxamic acid (AHA) is an effective inhibitor of urease, and it is readily excreted in urine. Herein, we report data regarding the efficacy of AHA in a rat model to prevent the pathologic sequelae of Proteus urinary infections.