RESUMEN
Guillain-Barré 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.
Asunto(s)
Bacteriófagos/crecimiento & desarrollo , Infecciones por Campylobacter/complicaciones , Campylobacter jejuni/patogenicidad , Gangliósidos/metabolismo , Síndrome de Guillain-Barré/microbiología , Factores de Virulencia/metabolismo , Infecciones por Campylobacter/inmunología , Infecciones por Campylobacter/microbiología , Campylobacter jejuni/genética , Campylobacter jejuni/inmunología , Campylobacter jejuni/virología , Biología Computacional , ADN Bacteriano/genética , Gangliósidos/inmunología , Humanos , Factores de Virulencia/inmunologíaAsunto(s)
Infecciones por Campylobacter/complicaciones , Campylobacter coli/inmunología , Síndrome de Guillain-Barré/microbiología , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Anticuerpos Antibacterianos/sangre , Técnicas de Tipificación Bacteriana , Infecciones por Campylobacter/microbiología , Campylobacter coli/clasificación , Campylobacter coli/genética , Campylobacter coli/aislamiento & purificación , Análisis por Conglomerados , Dermatoglifia del ADN , ADN Bacteriano/genética , Genotipo , Humanos , Epidemiología MolecularRESUMEN
Bacteria belonging to the species Campylobacter are the most common cause of bacterial diarrhoea in humans. The clinical phenotype associated with Campylobacter infections ranges from asymptomatic conditions to severe colitis and bacteremia. In susceptible patients, Campylobacter infections are associated with significant morbidity and mortality, with both host factors and bacterial factors being involved in the pathogenesis of bacteremia. In the host, age, gender and immune-compromising conditions may predispose for Campylobacter infections, whilst the most important bacterial determinants mentioned in the literature are cytotoxin production and flagellar motility. The role of sialylated lipo-oligosaccharide (LOS) and serum resistance in bacteremia is inconclusive at this time, and the clinical significance of Campylobacter bacteremia is not yet fully understood. More emphasis on the detection of Campylobacter species from blood cultures in susceptible patients at risk for Campylobacter infections will increase our understanding of the pathogenesis and the relevance of Campylobacter bacteremia.
RESUMEN
The main mechanisms by which Campylobacter jejuni causes diarrhea are unknown. In contrast to a recent communication, we report here the absence of an association with the plasmid pVir in patients infected with C. jejuni who developed bloody diarrhea in The Netherlands, and we suggest a role for other virulence determinants.