A novel link between Campylobacter jejuni bacteriophage defence, virulence and Guillain-Barr, syndrome

Rogier Louwen, Deborah A Horst - Kreft, AG de Boer, L van de Graaf, Gerjo Knegt, Marlies Hamersma, Astrid Heikema, AR Timms, B.C. Jacobs, JA Wagenaar, Hubert Endtz, J van der Oost, JM Wells, EES Nieuwenhuis, AHM (Arnoud) van Vliet, PTJ Willemsen, P van Baarlen, Alex Belkum

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Abstract

Guillain-Barr, syndrome (GBS) is a post-infectious disease in which the human peripheral nervous system is affected after infection by specific pathogenic bacteria, including Campylobacter jejuni. GBS is suggested to be provoked by molecular mimicry between sialylated lipooligosaccharide (LOS) structures on the cell envelope of these bacteria and ganglioside epitopes on the human peripheral nerves, resulting in autoimmune-driven nerve destruction. Earlier, the C. jejuni sialyltransferase (Cst-II) was found to be linked to GBS and demonstrated to be involved in the biosynthesis of the ganglioside-like LOS structures. Apart from a role in pathogenicity, we report here that Cst-II-generated ganglioside-like LOS structures confer efficient bacteriophage resistance in C. jejuni. By bioinformatic analysis, it is revealed that the presence of sialyltransferases in C. jejuni and other potential GBS-related pathogens correlated significantly with the apparent degeneration of an alternative anti-virus system: type II Clusters of Regularly Interspaced Short Palindromic Repeat and associated genes (CRISPR-Cas). Molecular analysis of the C. jejuni CRISPR-Cas system confirmed the bioinformatic investigation. CRISPR degeneration and mutations in the cas genes cas2, cas1 and csn1 were found to correlate with Cst-II sialyltransferase presence (p < 0.0001). Remarkably, type II CRISPR-Cas systems are mainly found in mammalian pathogens. To study the potential involvement of this system in pathogenicity, we inactivated the type II CRISPR-Cas marker gene csn1, which effectively reduced virulence in primarily cst-II-positive C. jejuni isolates. Our findings indicate a novel link between viral defence, virulence and GBS in a pathogenic bacterium.
Original languageUndefined/Unknown
Pages (from-to)207-226
Number of pages20
JournalEuropean Journal of Clinical Microbiology & Infectious Diseases
Volume32
Issue number2
DOIs
Publication statusPublished - 2013

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