Abstract

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studies have demonstrated that 26% of cystitis-associated E. coli and 35% of chronic pyelonephritis-associated E. coli (unpublished) but only 6% of those from asymptomatic bacteriuria and acute pyelonephritis carry genes of another type of adhesion, called Dr hemagglutinin.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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042029-03
Application #
2142053
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1992-02-01
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1996-01-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Texas Medical Br Galveston
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555

  Publications

Sledzi?ska, A; Mielech, A; Krawczyk, B et al. (2011) Fatal sepsis in a pregnant woman with pyelonephritis caused by Escherichia coli bearing Dr and P adhesins: diagnosis based on postmortem strain genotyping. BJOG 118:266-9
Wroblewska-Seniuk, Katarzyna; Nowicki, Stella; Le Bouguénec, Chantal et al. (2011) Maternal/fetal mortality and fetal growth restriction: role of nitric oxide and virulence factors in intrauterine infection in rats. Am J Obstet Gynecol 205:83.e1-7
Nowicki, B; Sledzinska, A; Samet, A et al. (2011) Pathogenesis of gestational urinary tract infection: urinary obstruction versus immune adaptation and microbial virulence. BJOG 118:109-12
Pawelczyk, Edyta; Nowicki, Bogdan J; Izban, Michael G et al. (2010) Spontaneous preterm labor is associated with an increase in the proinflammatory signal transducer TLR4 receptor on maternal blood monocytes. BMC Pregnancy Childbirth 10:66
Nowicki, Stella; Izban, Michael G; Pawelczyk, Edyta et al. (2009) Preterm labor: CD55 in maternal blood leukocytes. Am J Reprod Immunol 61:360-7
Rice, J C; Peng, T; Kuo, Y-F et al. (2006) Renal allograft injury is associated with urinary tract infection caused by Escherichia coli bearing adherence factors. Am J Transplant 6:2375-83
Rice, James C; Peng, Tao; Spence, Jeff S et al. (2005) Pyelonephritic Escherichia coli expressing P fimbriae decrease immune response of the mouse kidney. J Am Soc Nephrol 16:3583-91
Das, Margaret; Hart-Van Tassell, Audrey; Urvil, Petri T et al. (2005) Hydrophilic domain II of Escherichia coli Dr fimbriae facilitates cell invasion. Infect Immun 73:6119-26
Selvarangan, Rangaraj; Goluszko, Pawel; Singhal, Jyotsana et al. (2004) Interaction of Dr adhesin with collagen type IV is a critical step in Escherichia coli renal persistence. Infect Immun 72:4827-35
Johnson, James R; Stell, Adam L; O'Bryan, Timothy T et al. (2002) Global molecular epidemiology of the O15:K52:H1 extraintestinal pathogenic Escherichia coli clonal group: evidence of distribution beyond Europe. J Clin Microbiol 40:1913-23

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