Listeria monocytogenes internalins bind to the human intestinal mucin MUC2
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S H O R T CO M MU N I C A T I O N
Listeria monocytogenes internalins bind to the human intestinal mucin MUC2 Sara K. Lindén · Hélène Bierne · Christophe Sabet · Chin Wen Png · Timothy H Florin · Michael A. McGuckin · Pascale Cossart
Received: 11 January 2008 / Revised: 14 February 2008 / Accepted: 22 February 2008 / Published online: 8 March 2008 © Springer-Verlag 2008
Abstract Listeria monocytogenes cross the intestinal barrier causing systemic infections with high mortality rates. Intestinal infection triggers release of intestinal mucus. We show that three L. monocytogenes internalins, InlB, InlC and InlJ all bound to MUC2 (the major component of intestinal mucus), but not to the cell surface mucin MUC1. Binding was strongest to InlB>InlC>InlJ (P < 0.001). Listerial internalins are characterized by their internalin domain, composed by leucine rich repeats (LRR) followed by an immunogloblin-like region. We report here that the internalin domain of the InlJ protein also bound MUC2, suggesting that an internalin domain is suYcient to bind to MUC2.
Communicated by Erko Stackebrandt. S. K. Lindén · C. W. Png · T. H Florin · M. A. McGuckin (&) Mucosal Diseases Program, Mater Medical Research Institute, Level 3 Aubigny Place, Raymond Terrace, South Brisbane, QLD 4101, Australia e-mail: [email protected] S. K. Lindén e-mail: [email protected] H. Bierne · C. Sabet · P. Cossart Institut Pasteur, Unité des Interactions Bactéries-Cellules, 75015 Paris, France H. Bierne · C. Sabet · P. Cossart Inserm, U604, 75015 Paris, France H. Bierne · C. Sabet · P. Cossart INRA, USC2020, Paris 75015 Paris France T. H Florin Department of Medicine, University of Queensland, Brisbane, QLD 4065, Australia
Keywords MUC1
Listeria · LRR · Mucin · Mucus · MUC2 ·
Abbreviations LRR Leucine-rich repeats Inl Internalin MucBP MUCin-binding protein
Introduction Most human pathogens cause disease by attaching to, then crossing or disrupting mucosal surfaces (Linden et al. 2008). The gastrointestinal tract is lined by a protective mucus layer formed by mucin glycoproteins, which continuously wash the mucosal surfaces (Linden et al. 2008). In the small intestine and colon, MUC2 is the main secreted mucin making up the mucus layer. Under the mucus layer, the cell-surface mucins are a dominant feature of the apical surface of all mucosal epithelial cells. Mucins act as receptor molecules for pathogenic microorganisms and act as receptor decoys for pathogenic bacteria (Linden et al. 2004). Listeria monocytogenes is present as a commensal in the intestine of 1–10% of humans. During infection, the pathogen crosses the intestinal barrier and may cause bacteremia, meningitis or encephalitis in immunocompromized individuals, or foetal infections in pregnant women. The low prevalence of listeriosis indicates that host barrier function against this pathogen is normally highly eVective. Following inoculation of rat ileal loops, L. monocytogenes are observed within intestinal mucus (likely to be MUC2) (Pron et al. 1998). In vitro L. monocyto
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