Mechanisms Underlying Campylobacter fetus Pathogenesis in Humans: Surface‐Layer Protein Variation in Relapsing Infections
1Departments of Medicine and Microbiology, New York University School of Medicine, and 2Department of Veterans Affairs Medical Center, New York, New York; 3Département de Microbiologie et Infectiologie, Hôpital St‐Luc du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Campylobacter fetus causes gastrointestinal and systemic infections in humans. Although relapse is common despite antibiotic treatment, the mechanisms are not well understood. The surface‐layer proteins (SLPs) of C. fetus, which are critical in virulence, undergo high‐frequency phenotypic switching due to recombination of sap homologues, resulting in antigenic variation. To investigate the mechanisms involved in relapsing C. fetus infections, we compared SLP variation in 4 pairs of C. fetus strains that infect humans; initial and follow‐up isolations were performed 20 days to 34 months apart. Of the 4 pairs of strains, 2 had antigenic variation, and another provided evidence for selection for SLP‐positive populations. Southern hybridization indicated recombination underlying the SLP variation and up‐regulation. The fourth pair had the same SLP antigenic profile and sap homologue hybridization pattern, which is consistent with latency of the original strain in a privileged locus. In total, these findings indicate that relapse may reflect at least 3 differing pathogenetic pathways.
Received 29 July 2004; accepted 26 January 2005; electronically published 5 May 2005.
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Presented in part: 104th General Meeting of American Society for Microbiology, New Orleans, 23–17 May 2004 (abstract D‐089).
Financial support: National Institutes of Health (grant R01 AI24145); Medical Research Service of the Department of Veterans Affairs; Filomena M. D’Agostino Foundation.