ROLE OF BACTERIAL LECTINS IN KIDNEY DISEASES

点击翻译按钮获取中文摘要

Cystitis is the most common entity of urinary tract diseases, accounting for 1% of all office visits in the USA. Cystitis may lead to pyelonephritis, which is one of the main causes of end stage kidney disease. Escherichia coli is the most common pathogen of human urinary tract infection (UTI). Association of bacterial properties and clinical form of infection led to the discovery of P fimbriae as a virulence factor in acute pyelonephritis. P adhesions mediate attachment of E. coli to Gal-Gal rich receptors in the kidney tissue. Inhibition of attachment protects the kidney from colonization. Despite several efforts, a similar association has not been described for cystitis and chronic (CHP) pyelonephritis. Our recent studies have demonstrated that 26% of cystitis-associated E. coli and 35% of chronic pyelonephritis-associated E. coli (unpublished) but only 6% of those from asymptomatic bacteriuria and acute pyelonephritis carry genes of another type of adhesion, called Dr hemagglutinin. Dr hemagglutinin may attach to Dr receptor in UT and thereby allow bacterial colonization. Inhibition of the tissue-adhesion interaction might protect UT against colonization by Dr+ E. coli and prevent UT. At this time the contribution of Dr hemagglutinin and Dr receptors to pathogenicity of cystitis and chronic pyelonephritis has not been well documented. The proposed research will: (1) determine the locations of Dr receptors in tissues from different mouse strains; (2) quantitate the Dr receptor content in tissues of selected mouse strains; (3) construct Dr negative mutant of the clinical E. coli strain IH 11128; (4) determine the relative capacity of the Dr negative IH 11128 and Dr positive parent strain to colonize UT in a mouse model of ascending UTI; (5) determine persistence and pathogenesis of UTI induced by Dr positive E. coli in order to develop a model of chronic pyelonephritis; (6) further characterize epidemiology and properties of Dr+ E. coli by genotypic and phenotypic analysis.