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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.

Wild-type Campylobacter fetus strains possess high-molecular-weight S-layer proteins (S+) and are highly resistant to serum-mediated killing and phagocytosis. Spontaneous mutant strains lacking these proteins (S-) are serum and phagocytosis sensitive and have reduced virulence in a mouse model. Intact S+ cells were treated with pronase, which made them S- although genotypically S+ and had essentially no effect on other cellular proteins or on viability. Treatment with pronase, but not buffer alone, rendered these cells serum and phagocytosis sensitive and reduced mouse virulence to the level observed for the S- mutant cells. In related studies, purified S-layer proteins diminished neutrophil chemoluminescent responses to a heterologous particulate antigen. Finally, passive administration of antiserum to the 97-kDa S-layer protein partially protected mice against lethal challenge with the S+ strain. These studies define the contribution of the S-layer proteins to C. fetus virulence.

A HEp-2 cell culture model was used to investigate the antigens required for epithelial cell penetration by Campylobacter jejuni. Penetration of HEp-2 epithelial cells by C. jejuni was significantly inhibited (P less than .05) with C. jejuni lysate and a monoclonal antibody (MAb 1B4) in competitive inhibition assays. Immunogold electron microscopy revealed that MAb 1B4 bound to the flagella and cell surface of low-passage (invasive) C. jejuni M 96, whereas only the flagella of high-passage (noninvasive) C. jejuni M 96 were labeled. Western blot analysis revealed that MAb 1B4 identified an epitope on antigens of 64-44 kDa in lysates prepared from invasive and noninvasive isolates. In addition, antigens of 42-38 kDa were recognized in lysates prepared from only invasive C. jejuni strains. Proteinase K and sodium meta-periodate chemical treatment of C. jejuni M 96 lysate changed the mobility of antigens recognized by MAb 1B4. The increase in mobility demonstrated a decrease in size of molecules and suggested that antigens required for HEp-2 cell invasion by Campylobacter species may be glycoprotein in nature.

Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain.

Campylobacter fetus subspecies fetus causes both systemic and diarrheal illnesses. We studied 38 strains of C. fetus isolated from 34 patients; underlying illness was present in eight (89%) of nine patients with only systemic isolates compared with three (20%) of 15 patients with only fecal isolates (P = .002). In a standardized assay of susceptibility to normal human serum, 27 (71%) strains were resistant, six (16%) had intermediate susceptibility, and five (13%) were serum sensitive. Major protein bands migrating at 100 kDa or 125 kDa on polyacrylamide gels were present in all of the 25 serum-resistant strains tested but in only four of seven serum-sensitive isolates of C. fetus from humans and animals (P = .007). The presence of these bands was associated with type A lipopolysaccharide. A low-passaged strain, 82-40, was serum resistant and contained the 100-kDa protein; however, a spontaneous mutant of this strain lacked this band and was serum sensitive. The 100-kDa and 125-kDa proteins of three strains of C. fetus were antigenically cross reactive or identical and were exposed on the surface of the C. fetus cell. Serum resistance is inherent to most C. fetus isolates from humans and is associated with the presence of cross-reactive surface proteins.