Can Campylobacter coli induce Guillain-Barré syndrome?

Campylobacter jejuni enteritis is the most frequently identified infection preceding the Guillain-Barr\ue9 syndrome (GBS) and neural damage is thought to be induced through molecular mimicry between C. jejuni lipo-oligosaccharide (LOS) and human gangliosides. It has been questioned whether or not other Campylobacter species, including C. curvus, C. upsaliensis and C. coli, could be similarly involved. This is relevant because it would imply that bacterial factors considered important in the aetiology of GBS crossed species barriers. Two prior reports have appeared where C. coli was putatively associated with a case of GBS.Peer reviewed: YesNRC publication: Ye

Peptidoglycan-Modifying Enzyme Pgp1 Is Required for Helical Cell Shape and Pathogenicity Traits in Campylobacter jejuni

The impact of bacterial morphology on virulence and transmission attributes of pathogens is poorly understood. The prevalent enteric pathogen Campylobacter jejuni displays a helical shape postulated as important for colonization and host interactions. However, this had not previously been demonstrated experimentally. C. jejuni is thus a good organism for exploring the role of factors modulating helical morphology on pathogenesis. We identified an uncharacterized gene, designated pgp1 (peptidoglycan peptidase 1), in a calcofluor white-based screen to explore cell envelope properties important for C. jejuni virulence and stress survival. Bioinformatics showed that Pgp1 is conserved primarily in curved and helical bacteria. Deletion of pgp1 resulted in a striking, rod-shaped morphology, making pgp1 the first C. jejuni gene shown to be involved in maintenance of C. jejuni cell shape. Pgp1 contributes to key pathogenic and cell envelope phenotypes. In comparison to wild type, the rod-shaped pgp1 mutant was deficient in chick colonization by over three orders of magnitude and elicited enhanced secretion of the chemokine IL-8 in epithelial cell infections. Both the pgp1 mutant and a pgp1 overexpressing strain – which similarly produced straight or kinked cells – exhibited biofilm and motility defects. Detailed peptidoglycan analyses via HPLC and mass spectrometry, as well as Pgp1 enzyme assays, confirmed Pgp1 as a novel peptidoglycan DL-carboxypeptidase cleaving monomeric tripeptides to dipeptides. Peptidoglycan from the pgp1 mutant activated the host cell receptor Nod1 to a greater extent than did that of wild type. This work provides the first link between a C. jejuni gene and morphology, peptidoglycan biosynthesis, and key host- and transmission-related characteristics

Identification of Gene Networks and Pathways Associated with Guillain-Barré Syndrome

BACKGROUND: The underlying change of gene network expression of Guillain-Barré syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. METHODS AND FINDINGS: Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05). FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. CONCLUSIONS: This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies

Sialylation of Campylobacter jejuni lipo-oligosaccharides is associated with severe gastro-enteritis and reactive arthritis

We used various genotyping methods to identify bacterial genetic markers for development of arthritic symptoms following Campylobacter enteritis. We genotyped a collection of population derived Campylobacter strains, with detailed information on clinical characteristics, including arthritic symptoms. Besides using whole genome screening methods, we focused on the lipo-oligosaccharide (LOS) gene locus in which marker genes for developing post-Campylobacter neurological disease are present. Patients with arthritic symptoms were more frequently infected with Campylobacter jejuni strains with a class A LOS locus. We also found that patients who were infected with a C. jejuni strain containing sialic acid-positive LOS (class A, B or Q more frequently had bloody diarrhoea and a longer duration of symptoms. Furthermore, the IgM antibody response against Campylobacter was stronger in patients with a sialic acid containing LOS. Ganglioside auto-antibodies were observed in a small number of patients following infection with a class C strain. We conclude that sialylation of C. jejuni LOS is not only a risk factor for development of post-infectious symptoms, but is also associated with increased severity of enteric disease. (C) 2009 Elsevier Masson SAS. All rights reserved