Campylobacter fetus is recognized as a cause of systemic illness in persons with pre-existing conditions such as immunosuppression, infancy, liver disease, malignancy, or diabetes mellitus. It has been reported to cause meningitis, septic abortion, peritonitis, abscesses, bacteremia, endocarditis, and septic thrombophlebitis in humans. In ungulates (the natural host of this infection) C. fetus causes chronic genito-urinary tract infections that may be venereally transmitted. Dr. Blaser has identified a family of surface layer proteins (SAP) of different sizes and antigenicity that are responsible for C. fetus virulence. SAP+ C. fetus strains are serum and phagocytic resistant, and become bacteremic in mice whereas SAP- strains are sensitive to serum and phagocytic killing. The two serotypes (A and B) have been recognized based on lipopolysaccharide (LPS) characteristics. SAP from type A and type B cells differ in N-terminus, pI, and specificity of binding to LPS. Attachment of SAP to the cell- surface is dependent on divalent cations. C. fetus produce multiple tightly clustered homologs of sapA which encodes a 97 kDa SLP, each encoding a full-length SLP with sequence identity in the first 600 bp of the gene. The ORF becomes increasingly diverse in the 3' direction, but after the transcriptional terminator there is a short region of identity. Antigenic variation is due to rearrangement of sapA homologs involving reciprocal recombination. sapA expression is driven by a unique promoter present on a 6 kb inevitable element.
The aims of the current study are to (1) better characterize the frequency of the inversion phenomenon, confirm its RecA dependence, and investigate the conservation phenomenon among strains and the conservation of elements, (2) to define the functional elements permitting inversion, and (3) to characterize non-inversion mechanisms for antigenic variation. RNA- based mechanisms of antigenic variation will also be determined by comparison of genomic DNA and mRNA.
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