Biomolecule sulphation and novel methylations related to Guillain-Barré syndrome-associated Campylobacter jejuni serotype HS:19

Abstract

Campylobacter jejuni strains that produce sialylated lipooligosaccharides (LOS) can cause the immune-mediated disease Guillain-Barré syndrome (GBS). The risk of GBS after infection with C. jejuni Penner serotype HS:19 is estimated to be at least six times higher than the average risk. Aside from LOS biosynthesis genes, genomic characteristics that promote an increased risk for GBS following C. jejuni HS:19 infection, remain uncharacterized. We hypothesized that strains with the HS:19 serotype have unique genomic features that explain the increased risk for GBS. We performed genome sequencing, alignments, single nucleotide polymorphisms' analysis and methylome characterization on a subset, and pan-genome analysis on a large number of genomes to compare HS:19 with non-HS:19 C. jejuni genome sequences. Comparison of 36 C. jejuni HS:19 with 874 C. jejuni non-HS:19 genome sequences led to the identification of three single genes and ten clusters containing contiguous genes that were significantly associated with C. jejuni HS:19. One gene cluster of seven genes, localized downstream of the capsular biosynthesis locus, was related to sulphation of biomolecules. This cluster also encoded the campylobacter sialyl transferase Cst-I. Interestingly, sulphated bacterial biomolecules such as polysaccharides can promote immune responses and, therefore, (in the presence of sialic acid) may play a role in the development of GBS. Additional gene clusters included those involved in persistence-mediated pathogenicity and gene clusters involved in restriction-modification systems. Furthermore, characterization of methylomes of two HS:19 strains exhibited novel methylation patterns (5′-CATG-3 and 5′-m6AGTNNNNNNRTTG-3) that could differentially effect gene-expression patterns of C. jejuni HS:19 strains. Our study provides novel insight into specific genetic features and possible virulence factors of C. jejuni associated with the HS:19 serotype that may explain the increased risk of GBS.