Project Details


DESCRIPTION (Adapted from the Applicant's Abstract): Campylobacter fetus is a
pathogen of humans and animals. All wildtype C. fetus strains possess regular,
paracrystalline high molecular weight (97, 127, or 149kDa) surface layer
proteins (SLPs) that are critical for virulence. The SLPs inhibit complement
binding, which leads to both serum and phagocytosis resistance, and they
undergo antigenic variation. C. fetus cells possess 8 or 9 homologs of sapA,
which encodes a 97 kDa SLP. The homologs share multiple areas of homology with
each other, are clustered on the bacterial genome, and together with an
invertible region (IR) of 6kb form the sap locus. The investigators previously
showed that the DNA rearrangement (inversion) plays a major (if not exclusive)
role in the antigenic variation, and that mutation of recA removed all
detectable variation. They now have developed animal models to examine SLP
variation, have shown that antigenic variation due to sap locus recombination
occurs in recA strains, and have moved the IR onto the E. coli chromosome. The
first aim of the proposed work is to identify the recombination pathways that
permit the sap locus inversion. Their hypothesis is that the inversion depends
on conserved recombination genes including those in the RecBCD, RecE, and RecF
pathways. Alternatively, they might find that C. fetus has species-specific
recombination pathways. The ultimate goal will be to define and mutate the
recombination genes in C. fetus and examine the phenotypes of mutants. Their
second aim is to define the structural features present in the sapA homologs
that are required for recombination to occur. They propose to complete the map
of the sap locus and to create mutants that will permit assessment of the
necessary structural features. As part of this goal, they plan to identify the
sites of double strand breaks that are the initial sites for DNA strand
exchange. The third aim is to examine sap rearrangement in vivo in mice. After
establishing the model, they can examine the role of host responses in
directing the evolution of antigenic variation, and the fitness of defined
mutants. Finally, the data generated can be used to develop a mathematical
model of antigenic variation that focuses on the relationship between microbial
recombination generating diversity and host selection determining the direction
of change.
Effective start/end date12/31/895/31/06


  • National Institute of Allergy and Infectious Diseases: $281,427.00
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases: $288,750.00
  • National Institute of Allergy and Infectious Diseases: $288,750.00


  • Genetics
  • Molecular Biology
  • Hepatology


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