A capsular methyltransferase and an aminotransferase are associated with serum complement resistance in Campylobacter jejuni

Background: The outer surface capsule of Campylobacter jejuni protects the bacterium from complement-mediated killing. However, complement sensitivity often occurs within strains that possess identical capsular serotypes. The objective of this study was to determine whether phase-variable genes involved in capsule biosynthesis steer complement-mediated immunity.

Methods: Knock-out mutants of five phase-variable capsular genes generated in C. jejuni strain 11168H (serotype HS:2), were tested in complement killing assays. Serum IgG deposition was measured and the presence of the capsule was assessed using Alcian blue staining. Capsule loci of seven clinical HS:2 isolates were sequenced to assess these phase variable genes.

Results: Knock-out mutants of gene cj1426, a methyltransferase and gene cj1437, an aminotransferase, resulted in clear zones due to complement-mediated killing when bacteria were exposed to 50%, 25% or 12.5% serum. Already at 50% serum, overgrown zones were observed for the remaining knock-out mutants and the wild type strain. Enhanced IgG deposition was observed for strain Δcj1437, but not strain Δcj1426, suggesting that different complement pathways are affected by phase-variation in different C. jejuni capsule genes. Alcian blue staining demonstrated that a capsule was produced by all five knock-out mutants. Sequencing revealed that 4/7 and 3/7 clinical C. jejuni isolates had a predominant ‘phase off ’ state for genes cj1426 and Cj1437 respectively.

Conclusions: Disruption of a capsular methyltransferase and aminotransferase gene in C. jejuni strain 11168H resulted in a phenotypic switch from complement resistance to complement sensitive. However, strain variants that do not express the methyltransferase or aminotransferase may still cause disease.