This is a resubmission of a proposal to characterize the origin of multidrug-resistant clones of E. coli associated with urinary tract infections (UTI). Community-acquired multidrug-resistant UTI is an emerging drug-resistant infectious disease problem worldwide. Our recent studies suggest that drug resistant UTI prevalence in a community can suddenly increase by the introduction of a clonal group of drug-resistant E. coli strains. In a population-based study in California, we found that strains of E. coil belonging to a single clonal group called CgA were responsible for 50% of drug-resistant UTI among women in a college campus. The same clonal group was identified among drug-resistant UTI E. coli isolates from two college campuses in Midwestern United States. We proposed that these strains were spread by contaminated food products. We also showed that drug resistance in these E. coli isolates is mediated by genetic elements called integrons that carry gene cassettes that encode antibiotic resistance. In this project, we wish to demonstrate that drug-resistant uropathogenic E. coli strains acquire their resistance determinants in the food animal reservoir exposed to subtherapeutic doses of antibiotics. We hypothesize that these cassettes are transferred from animal Enterobacteriaceae species to E. coli strains in the animal reservoir. These E. coli strains then cause UTI in women. We will first analyze our large collection of drug-resistant uropathogenic E. coli isolates obtained from population-based studies for integron prevalence, class, and distribution, as well as for cassette type and sequences. We will then compare these cassette sequences to those of well-characterized multidrug-resistant animal E. coli isolates, as well as multidrug-resistant Salmonella typhimurium DT104 isolates. These findings should identify not only the distribution and extent of drug resistance determinants in major pathogenic Enteropacteriaceae species, but if our findings support the foodborne UTI hypothesis, we would be demonstrating that foodborne drug-resistant infectious disease problems in the United States are much greater in scope and disease spectrum than previously believed. This knowledge should lead to the implementation of improved control of drug-resistant infectious diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI059523-03
Application #
7151208
Study Section
Special Emphasis Panel (ZRG1-HOP-N (90))
Program Officer
Korpela, Jukka K
Project Start
2004-12-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
3
Fiscal Year
2007
Total Cost
$288,247
Indirect Cost
Name
University of California Berkeley
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Berman, Hillary F; Riley, Lee W (2013) Identification of novel antimicrobial resistance genes from microbiota on retail spinach. BMC Microbiol 13:272
Adams-Sapper, Sheila; Diep, Binh An; Perdreau-Remington, Francoise et al. (2013) Clonal composition and community clustering of drug-susceptible and -resistant Escherichia coli isolates from bloodstream infections. Antimicrob Agents Chemother 57:490-7
Adams-Sapper, S; Sergeevna-Selezneva, J; Tartof, S et al. (2012) Globally dispersed mobile drug-resistance genes in gram-negative bacterial isolates from patients with bloodstream infections in a US urban general hospital. J Med Microbiol 61:968-74
Raphael, Eva; Wong, Lisa K; Riley, Lee W (2011) Extended-spectrum Beta-lactamase gene sequences in gram-negative saprophytes on retail organic and nonorganic spinach. Appl Environ Microbiol 77:1601-7
Dias, Rubens C S; Moreira, Beatriz M; Riley, Lee W (2010) Use of fimH single-nucleotide polymorphisms for strain typing of clinical isolates of Escherichia coli for epidemiologic investigation. J Clin Microbiol 48:483-8
Ajiboye, Remi M; Solberg, Owen D; Lee, Bryan M et al. (2009) Global spread of mobile antimicrobial drug resistance determinants in human and animal Escherichia coli and Salmonella strains causing community-acquired infections. Clin Infect Dis 49:365-71
Dias, Rubens C S; Marangoni, Denise V; Riley, Lee W et al. (2009) Identification of uropathogenic Escherichia coli clonal group A (CgA) in hospitalised patients. Mem Inst Oswaldo Cruz 104:787-9
Dias, Rubens C S; Marangoni, Denise V; Smith, Sherry P et al. (2009) Clonal composition of Escherichia coli causing community-acquired urinary tract infections in the State of Rio de Janeiro, Brazil. Microb Drug Resist 15:303-8
Smith, Sherry P; Manges, Amee R; Riley, Lee W (2008) Temporal changes in the prevalence of community-acquired antimicrobial-resistant urinary tract infection affected by Escherichia coli clonal group composition. Clin Infect Dis 46:689-95
Loui, Cindy; Grigoryan, Grigor; Huang, Haohao et al. (2008) Bacterial communities associated with retail alfalfa sprouts. J Food Prot 71:200-4

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