Gene acquisition is crucial for the evolution and emergence of pathogenic bacteria. Traits acquired by pathogens enable them to survive in their reservoirs, and colonize and injure the hosts that they infect. Shiga toxin-producing E. coli (STEC), such as E. coli 0157:H7 and selected non-0157:H7 toxin-producing E. coli, provide a unique opportunity to study the evolutionary aspect of the acquisition of virulence traits. E. coli containing genes encoding Shiga toxins are phylogenetically diverse, but virulent strains are almost always found in two well defined phylogenetic clusters (STEC 1 and STEC 2 groups). The investigators propose to study systematically, using comparative genome analysis, the traits these pathogens have acquired, to determine the distribution of putative virulence loci, and to discern the sequence of acquisition of these traits. They will also assess the clonal nature of gene expression of these pathogens in bovids and humans. Data generated by this project will elucidate the mechanisms used by virulent organisms to accumulate the necessary genetic components to be successful pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI047499-05
Application #
6744221
Study Section
Special Emphasis Panel (ZRG1-GEN (01))
Program Officer
Sawyer, Leigh A
Project Start
1999-09-30
Project End
2005-08-31
Budget Start
2003-02-01
Budget End
2005-08-31
Support Year
5
Fiscal Year
2002
Total Cost
$239,010
Indirect Cost
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
El Feghaly, Rana E; Stauber, Jennifer L; Tarr, Phillip I et al. (2013) Intestinal inflammatory biomarkers and outcome in pediatric Clostridium difficile infections. J Pediatr 163:1697-1704.e2
Bielaszewska, Martina; Middendorf, Barbara; Tarr, Phillip I et al. (2011) Chromosomal instability in enterohaemorrhagic Escherichia coli O157:H7: impact on adherence, tellurite resistance and colony phenotype. Mol Microbiol 79:1024-44
Leopold, Shana R; Shaikh, Nurmohammad; Tarr, Phillip I (2010) Further evidence of constrained radiation in the evolution of pathogenic Escherichia coli O157:H7. Infect Genet Evol 10:1282-5
Leopold, Shana R; Magrini, Vincent; Holt, Nicholas J et al. (2009) A precise reconstruction of the emergence and constrained radiations of Escherichia coli O157 portrayed by backbone concatenomic analysis. Proc Natl Acad Sci U S A 106:8713-8
Bielaszewska, Martina; Prager, Rita; Vandivinit, Liz et al. (2009) Detection and characterization of the fimbrial sfp cluster in enterohemorrhagic Escherichia coli O165:H25/NM isolates from humans and cattle. Appl Environ Microbiol 75:64-71
Tarr, Cheryl L; Nelson, Adam M; Beutin, Lothar et al. (2008) Molecular characterization reveals similar virulence gene content in unrelated clonal groups of Escherichia coli of serogroup O174 (OX3). J Bacteriol 190:1344-9
Bielaszewska, Martina; Prager, Rita; Kock, Robin et al. (2007) Shiga toxin gene loss and transfer in vitro and in vivo during enterohemorrhagic Escherichia coli O26 infection in humans. Appl Environ Microbiol 73:3144-50
Shaikh, Nurmohammad; Holt, Nicholas J; Johnson, James R et al. (2007) Fim operon variation in the emergence of Enterohemorrhagic Escherichia coli: an evolutionary and functional analysis. FEMS Microbiol Lett 273:58-63
Qin, Xuan; Razia, Yasmin; Johnson, James R et al. (2006) Ciprofloxacin-resistant gram-negative bacilli in the fecal microflora of children. Antimicrob Agents Chemother 50:3325-9
Rashid, Rebecca A; Tarr, Phillip I; Moseley, Steve L (2006) Expression of the Escherichia coli IrgA homolog adhesin is regulated by the ferric uptake regulation protein. Microb Pathog 41:207-17

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