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.

Shotgun metagenomics of fecal samples from children in Peru reveals frequent complex co-infections with multiple Campylobacter species

“…When levels of Campylobacter were high, as seen for sample 150687 (S1B Fig), many distinct reads from around the genome were mapped. In fact, for samples with high read counts to a specific Campylobacter species, remapping the reads to diverse variable regions of the species from multiple strains, such as lipooligosaccharide and capsule biosynthesis loci [37][38][39], will provide additional details to the strains in the samples. At lower levels, where fewer reads were mapped, the reads discriminatory power needs to be addressed through BLASTn analysis and elimination of mapped reads that were associated with non-discriminatory regions like the rRNA loci or transposons.…”