THE PROJECT'S BROAD, LONG TERM OBJECTIVES are to define the contributions to the pathogenesis of ascending urinary tract infection UTI) of prototypic uropathogenic strain J96's enigmatic Class I and Class III variants of the Escherichia coli P firmbrial adhersin molecule PapG, and to delineate the geographic extent, host range, and disease associations of a J96-like clonal group of uropathogenic E. Coli whose members characteristically possess one or both of these PapG adhesins.
THE SPECIFIC AIMS are 1) to construct single and double- """"""""knockout"""""""" PapG mutants of a wildtype """"""""J96-like"""""""" E.coli strain and reconstituted derivates of each, and to evaluate their urovirulence in a mouse model of ascending UTI; and 2) to determine the relatedness ot prototypic uropathogenic strain J96 of carefully selected animal and human E.coli isolates from North America and Europe. EXPERIMENTAL DESIGN AND METHODS: PapG mutants will be constructed in """"""""J96-like"""""""" strain CP9 using a suicide plasmid allele exchange system and will be reconstituted for the appropriate papG genotype using recombinant papG plasmids. These derivatives will be tested for urovirulence in comparison with the wild-type parent strain in an established mouse model of ascending UTI. In addition, 225 clinical E.coli isolaates of serogroup O4 from known human and animal sources will be evaluated for similarities to J96 with respect to multiple differentiating characteristics through the use of polymerase chain reaction- (PCR-) based genomic ifingerprinting, O:K:H;F serotyping, and PCR-based detection of the three papG alleles and genes for cytotoxic necrotizing factor 1 (chf1) and aerobactin (aer). THE HEALTH RELATEDNESS OF THE PROJECT lies in the need for a better understanding of 1) the virulence mechanisms of the Ecoli strains that cause UTI, and 2) these strains' geographic distribution and pathogenic behavior. Such information will speed the development of preventive measures against UTI and related infections. Since the virulence of strain J96 has been extensively studied, further elucidation of J96's virulence mechanisms, and clarification of the clinical behavior of """"""""J96-like"""""""" strains, will extend the usefulness of the already-available information regarding strain J96.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK047504-05
Application #
2406423
Study Section
Special Emphasis Panel (ZRG4-GMB (05))
Project Start
1993-09-30
Project End
2001-08-31
Budget Start
1997-09-15
Budget End
1998-08-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Johnson, James R; Clabots, Connie; Rosen, Henry (2006) Effect of inactivation of the global oxidative stress regulator oxyR on the colonization ability of Escherichia coli O1:K1:H7 in a mouse model of ascending urinary tract infection. Infect Immun 74:461-8
Johnson, James R; Jelacic, Srdjan; Schoening, Laura M et al. (2005) The IrgA homologue adhesin Iha is an Escherichia coli virulence factor in murine urinary tract infection. Infect Immun 73:965-71
Johnson, James R; Scheutz, Flemming; Ulleryd, Peter et al. (2005) Host-pathogen relationships among Escherichia coli isolates recovered from men with febrile urinary tract infection. Clin Infect Dis 40:813-22
Johnson, James R; Kuskowski, Michael A; O'bryan, Timothy T et al. (2005) Virulence genotype and phylogenetic origin in relation to antibiotic resistance profile among Escherichia coli urine sample isolates from Israeli women with acute uncomplicated cystitis. Antimicrob Agents Chemother 49:26-31
Sannes, Mark R; Kuskowski, Michael A; Johnson, James R (2004) Antimicrobial resistance of Escherichia coli strains isolated from urine of women with cystitis or pyelonephritis and feces of dogs and healthy humans. J Am Vet Med Assoc 225:368-73
Johnson, James R; O'Bryan, Timothy T (2004) Detection of the Escherichia coli group 2 polysaccharide capsule synthesis Gene kpsM by a rapid and specific PCR-based assay. J Clin Microbiol 42:1773-6
Manges, Amee R; Johnson, James R; Riley, Lee W (2004) Intestinal population dynamics of UTI-causing Escherichia coli within heterosexual couples. Curr Issues Intest Microbiol 5:49-57
Sannes, Mark R; Kuskowski, Michael A; Johnson, James R (2004) Geographical distribution of antimicrobial resistance among Escherichia coli causing acute uncomplicated pyelonephritis in the United States. FEMS Immunol Med Microbiol 42:213-8
Russo, Thomas A; Johnson, James R (2003) Medical and economic impact of extraintestinal infections due to Escherichia coli: focus on an increasingly important endemic problem. Microbes Infect 5:449-56
Johnson, James R; Kaster, Nicholas; Kuskowski, Michael A et al. (2003) Identification of urovirulence traits in Escherichia coli by comparison of urinary and rectal E. coli isolates from dogs with urinary tract infection. J Clin Microbiol 41:337-45

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