Abstract

The objective of the proposed research is to define the clonal structure and genetic relationships among pathogenic strains of Escherichia coli that cause enteric disease in humans and animals, with special emphasis on strains that produce cytotoxins (shiga-like toxins or SLTs) that are functionally related to that of Shigella dysenteria. Genetic comparisons, based on the electrophoretic detection of allelic variation at enzyme- encoding genes, will be used to identify pathogenic clones and to establish the overall relatedness of SLT-producing strains to other established groups of pathogenic E. coli, such as strains of enteropathogenic serotypes that have long been associated with outbreaks of infantile diarrhea. A second related aim is to determine the allelic variation in shiga-like toxin genes, through the analysis of DNA polymorphisms using restriction enzymes that recognize four-nucleotide sequences, for the purpose of elucidating the spread of toxins genes into specific chromosomal backgrounds that results in new pathogenic forms.
A final aim i s to investigate the pattern of geographic spread of a newly described pathogenic clone (serotype 0157:H7) through the analysis of rapidly evolving insertion sequences. The results will be used to draw inferences regarding the role of specific chromosomal backgrounds in enteric disease and the genetic events underlying the origin of new pathogenic forms of E. coli.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Modified Research Career Development Award (K04)
Project #
5K04AI000964-02
Application #
3071001
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802

  Publications

Alvarez, Yelina; Tang, Xiaobin; Coligan, John E et al. (2008) The CD300a (IRp60) inhibitory receptor is rapidly up-regulated on human neutrophils in response to inflammatory stimuli and modulates CD32a (FcgammaRIIa) mediated signaling. Mol Immunol 45:253-8
Bokete, T N; Whittam, T S; Wilson, R A et al. (1997) Genetic and phenotypic analysis of Escherichia coli with enteropathogenic characteristics isolated from Seattle children. J Infect Dis 175:1382-9
Goncalves, A G; Campos, L C; Gomes, T A et al. (1997) Virulence properties and clonal structures of strains of Escherichia coli O119 serotypes. Infect Immun 65:2034-40
Rodrigues, J; Scaletsky, I C; Campos, L C et al. (1996) Clonal structure and virulence factors in strains of Escherichia coli of the classic serogroup O55. Infect Immun 64:2680-6
Kapur, V; Kanjilal, S; Hamrick, M R et al. (1995) Molecular population genetic analysis of the streptokinase gene of Streptococcus pyogenes: mosaic alleles generated by recombination. Mol Microbiol 16:509-19
Maslow, J N; Whittam, T S; Gilks, C F et al. (1995) Clonal relationships among bloodstream isolates of Escherichia coli. Infect Immun 63:2409-17
Campos, L C; Whittam, T S; Gomes, T A et al. (1994) Escherichia coli serogroup O111 includes several clones of diarrheagenic strains with different virulence properties. Infect Immun 62:3282-8
Boyd, E F; Nelson, K; Wang, F S et al. (1994) Molecular genetic basis of allelic polymorphism in malate dehydrogenase (mdh) in natural populations of Escherichia coli and Salmonella enterica. Proc Natl Acad Sci U S A 91:1280-4
White, D G; Dho-Moulin, M; Wilson, R A et al. (1993) Clonal relationships and variation in virulence among Escherichia coli strains of avian origin. Microb Pathog 14:399-409
Whittam, T S; Wolfe, M L; Wachsmuth, I K et al. (1993) Clonal relationships among Escherichia coli strains that cause hemorrhagic colitis and infantile diarrhea. Infect Immun 61:1619-29

Showing the most recent 10 out of 16 publications