Mechanisms underlying Campylobacter fetus pathogenesis in humans: surface-layer protein variation in relapsing infections.
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.
Tu
Zheng-Chao
ZC
Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
Gaudreau
Christiane
C
Blaser
Martin J
MJ
D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D002169:Campylobacter Infections / Q000382:microbiology*; D002168:Campylobacter fetus / Q000235:genetics* / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D010641:Phenotype; D012008:Recurrence
D001426:Bacterial Proteins; D008562:Membrane Glycoproteins; C055764:S-layer proteins