Campylobacter jejuni response to human mucin MUC2: modulation of colonization and pathogenicity determinants

Abstract

Campylobacter jejuni is the main cause of bacterial acute gastroenteritis worldwide. In its colonization of the host intestinal tract, it encounters secreted mucins in the mucus layer and surface mucins in the epithelial cells. Mucins are complex glycoproteins that comprise the major component of mucus and give mucus its viscous consistency. MUC2 is the most abundant secreted mucin in the human intestine; it is a major chemoattractant for C. jejuni, and the bacterium binds to it. There are no studies on the transcriptional response of the bacterium to this mucin. Here, cell-culture techniques and quantitative RT-PCR were used to characterize in vitro the effects of MUC2 on C. jejuni growth and the changes in expression of 20 C. jejuni genes related to various functions. The genes encoding cytolethal distending toxin protein (cdtABC), vacuolating cytotoxin (vacB), C. jejuni lipoprotein (jlpA), Campylobacter invasion antigen (ciaB), the multidrug efflux system (cmeAB), putative mucin-degrading enzymes (cj1344c, cj0843c, cj0256 and cj1055c), flagellin A (flaA) and putative rod-shape-determining proteins (mreB and mreC) were upregulated, whereas those encoding Campylobacter adhesion fibronectin-binding protein (cadF) and sialic acid synthase (neuB1) were downregulated. These results showed that C. jejuni utilizes MUC2 as an environmental cue for the modulation of expression of genes with various functions including colonization and pathogenicity. INTRODUCTIONCampylobacter jejuni is a Gram-negative, spiral, motile bacterium that colonizes the intestine of vertebrates. The bacterium is the main cause of human acute bacterial gastroenteritis in both developing and developed countries (Allos, 2001). Common symptoms of human C. jejuni infection are diarrhoea, fever, vomiting and abdominal pain. C. jejuni infection is a leading cause of childhood morbidity and mortality in the developing world (Allos, 2001). It is associated with the development of intestinal mucosa-associated lymphoid tissue lymphoma (Lecuit et al., 2004) and with post-infection autoimmune diseases such as Guillain-Barré and Miller Fisher syndromes (Yuki & Koga, 2006). Its various pathogenic effects indicate that C. jejuni infection poses a significant global public health problem.The mucosal tissues of the gastrointestinal, respiratory, urinary and reproductive tracts, as well as the surfaces of several organs such as the eye, nose and mouth, are exposed to the external environment. The mucus layer present in these tissues provides protection to underlying mucosal epithelial cells against chemical, enzymic, microbial and mechanical insult (Neutra & Forstner, 1987;Strugala et al., 2003). The major components of the mucus layer are secreted gel-forming mucins, complex glycoproteins that give mucus its viscous consistency.Most pathogenic bacteria that colonize the gastrointestinal tract subvert the mucus barrier by effective motility through the gel and the use of enzymes capable of degrading mucin carbohydrates and/or mucins. MUC2 is the most common gel-f...

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Campylobacter jejuniinduces extra-intestinal immune responses via toll-like-receptor-4 signaling in conventional IL-10 deficient mice with chronic colitis

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