Abstract

The first step in establishment of infectious diarrheal disease is the attachment of the invading pathogenic bacteria to the host tissue. In the case of enterotoxigenic Escherichia coli (ETEC), this is mediated by colonization factor antigens which constitute the major subunit of proteinaceous surface structures on the bacteria (pili or fimbriae). CFA/I, CFA/II and E8775 have been identified so far in human ETEC strains. CFA/II is composed of three separate antigens, called CSl, 2, and 3. These antigens are plasmid encoded, but their expression is regulated by the host and expression of CSl and CS2 is mutually exclusive. We propose to apply molecular techniques to the study of CFA/II antigens to learn about host regulation of plasmid-encoded functions. This work should lead to the understanding of the structure, assembly, genetic control and function of CS2 pili. We hope that the information gleaned will lead to a strategy for the development of a vaccine to protect against human ETEC strains or possibly to an adhesin analog therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024870-03
Application #
3138124
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1990-02-01
Budget End
1991-01-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Starks, Angela M; Froehlich, Barbara J; Jones, Tamara N et al. (2006) Assembly of CS1 pili: the role of specific residues of the major pilin, CooA. J Bacteriol 188:231-9
Froehlich, Barbara; Parkhill, Julian; Sanders, Mandy et al. (2005) The pCoo plasmid of enterotoxigenic Escherichia coli is a mosaic cointegrate. J Bacteriol 187:6509-16
Froehlich, Barbara; Holtzapple, Erik; Read, Timothy D et al. (2004) Horizontal transfer of CS1 pilin genes of enterotoxigenic Escherichia coli. J Bacteriol 186:3230-7
Munson, George P; Holcomb, Lisa G; Alexander, Heather L et al. (2002) In vitro identification of Rns-regulated genes. J Bacteriol 184:1196-9
Munson, G P; Holcomb, L G; Scott, J R (2001) Novel group of virulence activators within the AraC family that are not restricted to upstream binding sites. Infect Immun 69:186-93
Munson, G P; Scott, J R (2000) Rns, a virulence regulator within the AraC family, requires binding sites upstream and downstream of its own promoter to function as an activator. Mol Microbiol 36:1391-402
Engler, P; Storb, U (2000) A linkage map of distal mouse chromosome 4 in the vicinity of Ssm1, a strain-specific modifier of methylation. Mamm Genome 11:694-5
Munson, G P; Scott, J R (1999) Binding site recognition by Rns, a virulence regulator in the AraC family. J Bacteriol 181:2110-7
Sakellaris, H; Munson, G P; Scott, J R (1999) A conserved residue in the tip proteins of CS1 and CFA/I pili of enterotoxigenic Escherichia coli that is essential for adherence. Proc Natl Acad Sci U S A 96:12828-32
Sakellaris, H; Scott, J R (1998) New tools in an old trade: CS1 pilus morphogenesis. Mol Microbiol 30:681-7

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