1887

Abstract

strains that produce sialylated lipooligosaccharides (LOS) can cause the immune-mediated disease Guillain-Barré syndrome (GBS). The risk of GBS after infection with 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 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 genome sequences. Comparison of 36 HS:19 with 874 non-HS:19 genome sequences led to the identification of three single genes and ten clusters containing contiguous genes that were significantly associated with 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′-AGTNNNNNNRTTG-3) that could differentially effect gene-expression patterns of HS:19 strains. Our study provides novel insight into specific genetic features and possible virulence factors of associated with the HS:19 serotype that may explain the increased risk of GBS.

Funding
This study was supported by the:
  • USDA Agricultural Research Service (Award 2030-42000-055-00D)
    • Principle Award Recipient: T. ParkerCraig
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-11-01
2024-04-26
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