Abstract

Guerry and colleagues, in a first amendment to a new R01 application, propose to study the genetics of Campylobacter coli and C. jejuni genes responsible for post-translational glycosylation of flagellin. They propose that the modified surface-exposed protein plays a role in serospecificity of strains and serves as important antigens, potentially useful for vaccine development. The approach will include molecular genetic analysis of genes involved in sialic acid biosynthesis and addition of these residues to flagellin. In vitro invasion assays and animal (ferret and rabbit) models of infection will be used to assess virulence of C. coli and C. jejuni glycosylation-deficient mutants. There are three specific aims. 1. Complete the characterization of the post-translational modification genes of flagellin in C. coli VC167, and correlate the genetics with the structure of the post-translational modification; 2. Characterize and mutate sialic acid biosynthetic genes in two strains of C. jejuni, MSC57360 and 81-176; and 3. Measure the virulence and immunogenicity of mutants of VC167, MSC, and 81-176 which are defective in post-translational modification genes and/or have non-sialylated LPS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043559-02
Application #
6170564
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1999-07-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
2
Fiscal Year
2000
Total Cost
$172,647
Indirect Cost

  Institution

Name
Henry M. Jackson Fdn for the Adv Mil/Med
Department
Type
DUNS #
City
Rockville
State
MD
Country
United States
Zip Code
20817

  Publications

Ewing, Cheryl P; Andreishcheva, Ekaterina; Guerry, Patricia (2009) Functional characterization of flagellin glycosylation in Campylobacter jejuni 81-176. J Bacteriol 191:7086-93
Yokoyama, Takeshi; Paek, Seonghee; Ewing, Cheryl P et al. (2008) Structure of a sigma28-regulated nonflagellar virulence protein from Campylobacter jejuni. J Mol Biol 384:364-76
Galkin, Vitold E; Yu, Xiong; Bielnicki, Jakub et al. (2008) Divergence of quaternary structures among bacterial flagellar filaments. Science 320:382-5
Guerry, Patricia (2007) Campylobacter flagella: not just for motility. Trends Microbiol 15:456-61
Poly, Frederic; Ewing, Cheryl; Goon, Scarlett et al. (2007) Heterogeneity of a Campylobacter jejuni protein that is secreted through the flagellar filament. Infect Immun 75:3859-67
Guerry, Patricia; Ewing, Cheryl P; Schoenhofen, Ian C et al. (2007) Protein glycosylation in Campylobacter jejuni: partial suppression of pglF by mutation of pseC. J Bacteriol 189:6731-3
McNally, David J; Aubry, Annie J; Hui, Joseph P M et al. (2007) Targeted metabolomics analysis of Campylobacter coli VC167 reveals legionaminic acid derivatives as novel flagellar glycans. J Biol Chem 282:14463-75
Guerry, Patricia; Ewing, Cheryl P; Schirm, Michael et al. (2006) Changes in flagellin glycosylation affect Campylobacter autoagglutination and virulence. Mol Microbiol 60:299-311
Goon, Scarlett; Ewing, Cheryl P; Lorenzo, Maria et al. (2006) A sigma28-regulated nonflagella gene contributes to virulence of Campylobacter jejuni 81-176. Infect Immun 74:769-72
McNally, David J; Hui, Joseph P M; Aubry, Annie J et al. (2006) Functional characterization of the flagellar glycosylation locus in Campylobacter jejuni 81-176 using a focused metabolomics approach. J Biol Chem 281:18489-98

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