Enteropathogenic Escherichia coil (EPEC) are an important cause of diarrhea in infants. The long- term objectives of this project are to understand the pathogenesis of disease due to this organism. Previous work on this project has resulted in the discovery of a 35 kb pathogenicity island called the Locus of Enterocyte Effacement (LEE) that is responsible for the attaching and effacing (AE) histopathology on intestinal epithelial cells that is the hallmark of EPEC infections. The LEE island encodes the epithelial cell adhesin named intimin, a type III protein secretion system, and several effector proteins that are translocated into epithelial cells to mediate the AE lesion. Typical EPEC strains possess the LEE plus the EAF plasmid that encodes a type IV pilus (BFP) that contributes to epithelial cell adherence and a positive regulator of EPEC virulence factors called Per. Typical EPEC strains are an important cause of infant diarrhea in developing countries but are infrequent causes of disease in the U.S. Atypical EPEC strains contain the LEE but lack the EAF plasmid. In contrast to typical EPEC strains, atypical EPEC appear to cause outbreaks and sporadic disease in adults in industrialized countries such as the U.S., Finland, and Japan. Recent studies of atypical EPEC in children with diarrhea in the U.S. suggest that the incidence of infections with this pathogen may equal or exceed that of Salmonella, Shigella, Campylobacter, or E. coil O157:H7. The proposed research goals for the next period of support include continued characterization of pathogenic mechanisms of typical EPEC strains, particularly genes encoded outside the LEE, and a new focus on potential pathogenic mechanisms of atypical EPEC.
The specific aims are 1) Characterize the Long Polar Fimbriae (LPF) of EPEC and assess in viVo expression of this and other potential adhesins;2) Identify and characterize genes regulated by the Ler and Per regulators of EPEC virulence factors using genomic arrays;3) Characterize human host epithelial cell transcriptional responses to EPEC infection using in vitro organ culture (IVOC);and 4) CharacteriZe potential virulence factors in atypical EPEC strains.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI021657-27
Application #
8223298
Study Section
Special Emphasis Panel (NSS)
Program Officer
Baqar, Shahida
Project Start
1986-07-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
27
Fiscal Year
2012
Total Cost
$521,151
Indirect Cost
$157,923
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Steyert, Susan R; Rasko, David A; Kaper, James B (2011) Functional and phylogenetic analysis of ureD in Shiga toxin-producing Escherichia coli. J Bacteriol 193:875-86
Rhee, Ki-Jong; Cheng, Hao; Harris, Antoneicka et al. (2011) Determination of spatial and temporal colonization of enteropathogenic E. coli and enterohemorrhagic E. coli in mice using bioluminescent in vivo imaging. Gut Microbes 2:34-41
Habdas, Benjamin J; Smart, Jennifer; Kaper, James B et al. (2010) The LysR-type transcriptional regulator QseD alters type three secretion in enterohemorrhagic Escherichia coli and motility in K-12 Escherichia coli. J Bacteriol 192:3699-712
Schuller, Stephanie; Lucas, Mark; Kaper, James B et al. (2009) The ex vivo response of human intestinal mucosa to enteropathogenic Escherichia coli infection. Cell Microbiol 11:521-30
Hansen, Anne-Marie; Kaper, James B (2009) Hfq affects the expression of the LEE pathogenicity island in enterohaemorrhagic Escherichia coli. Mol Microbiol 73:446-65
Lodato, Patricia B; Kaper, James B (2009) Post-transcriptional processing of the LEE4 operon in enterohaemorrhagic Escherichia coli. Mol Microbiol 71:273-90
Mousnier, Aurelie; Whale, Andrew D; Schuller, Stephanie et al. (2008) Cortactin recruitment by enterohemorrhagic Escherichia coli O157:H7 during infection in vitro and ex vivo. Infect Immun 76:4669-76
Frankel, Gad; Phillips, Alan D (2008) Attaching effacing Escherichia coli and paradigms of Tir-triggered actin polymerization: getting off the pedestal. Cell Microbiol 10:549-56
Bai, Li; Schuller, Stephanie; Whale, Andrew et al. (2008) Enteropathogenic Escherichia coli O125:H6 triggers attaching and effacing lesions on human intestinal biopsy specimens independently of Nck and TccP/TccP2. Infect Immun 76:361-8

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