GENOMIC CHARACTERIZATION OF CAMPYLOBACTER JEJUNI BD-67: A HIGHLY PATHOGENIC STRAIN ASSOCIATED WITH SEVERE FORM OF GUILLAIN- BARRÉ SYNDROME

Abstract

Intro: Campylobacter jejuni is the leading cause of gastroenteritis and associated with Guillain-Barré syndrome (GBS) in both developed and developing countries. We provided distinct genomic features of a highly pathogenic C. jejuni strain, BD-67, associated with severe axonal variant of GBS. Methods: C. jejuni BD-67 strain was isolated from stool sample of GBS patient in Bangladesh and sequenced in Illumina NextSeq-500 platform. The genome was analyzed using multiple bioinformatics approaches. Auto-antibodies were measured by enzyme-linked immunosorbent assays (ELISAs). Findings: C. jejuni BD-67 was associated with severe axonal form of GBS (GBSDS 4; [bed bound] with ophthalmoplegia and reached nadir on day 6. Patient was serologically positive for C. jejuni LOS, GM1, GD1a, and GQ1b antibodies. C. jejuni BD-67 genome exhibited uniqueness in potential virulent genes of lipooligosaccharide (LOS) region, phage integration, and glycosyltransferase genes. BD-67 strain exhibited penner-serotype HS:23 and LOS class B. In-silico multilocus sequence typing (MLST) exhibited BD-67 belongs to sequence-type ST-985 and clonal complex ST-403 that appeared as the most diverse node in MLST-based minimum spanning tree analysis. Comparative analysis of LOS cluster and its components demonstrated that the β-1,3-glycosyltransferase and β-1,4-N-acetylgalactosaminyltransferase genes of LOS were truncated and produce 3 & 2 truncated complete DNA sequences (CDSs), respectively. The cstII gene was highly diversified with amino acid identity of 90.41% and belongs to a distinct clade with BD-10 in global phylogeny. BD-67 strain harbored 2 C. jejuni integrated elements (CJIE1 and CJIE3) which is rare in GBS-associated C. jejuni strains. Pangenomic analysis unveiled the presence of a unique genomic region in BD-67 which encoded different glycosyltransferase genes, phage integration (intA), flagellar protein (flgE_1). Conclusion: The atypical virulence factors, truncated CDSs of LOS cluster, and different unique structural genes of BD-67 might be associated with the severe form of GBS. Multi-omics study may unveil the key of C. jejuni associated GBS pathogenesis and severity.