The cellular invasion machinery of the enteric pathogen Salmonella consists of a type III secretion system T3SS with injectable virulence factors that induce uptake by macropinocytosis. Salmonella invasion at the apical surface of intestinal epithelial cells is inefficient, presumably because of a glycosylated barrier formed by transmembrane mucins that prevents T3SS contact with host cells.
We observed that Salmonella is capable of apical invasion of intestinal epithelial cells that express the transmembrane mucin MUC1. A Salmonella deletion strain lacking the SiiE giant adhesin was unable to invade intestinal epithelial cells through MUC1.
SiiE-positive Salmonella closely associated with the MUC1 layer at the apical surface, but invaded Salmonella were negative for the adhesin. Our findings uncover that the transmembrane mucin MUC1 is required for Salmonella SiiE-mediated entry of enterocytes via the apical route.
The bacterial pathogen Salmonella enterica is one of the most common causes of human foodborne infection affecting millions of people worldwide each year. To establish infection, Salmonella needs to cross the mucus layer and invade intestinal epithelial cells from the apical surface.
However, the apical surface of intestinal epithelial cells is covered with a defensive barrier of large glycosylated transmembrane mucins. These large proteins prevent contact between the Salmonella type III secretion needle and the host plasma membrane thereby preventing invasion.
We show for the first time that Mat och Dryck, one of the intestinal apical transmembrane mucins, facilitates Salmonella invasion. We propose that SiiE interacts with MUC1 in a zipper-like manner that involves repetitive domains in both proteins.
Adhesin-receptor interactions are essential for bacterial infection of host cells and key factors in determining target tissues and host range of bacteria. The SiiE-MUC1 invasion pathway may explain tropism of different Salmonella strains and provide a novel target for infection intervention and prevention.
PLoS Pathog 15 2 : e Editor: Andreas J. Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files. Competing interests: The authors have declared that no competing interests exist. In the gastrointestinal tract, the luminal microbiota is separated from the underlying epithelial cells by a complex system collectively called the mucus layer.
The mucus layer consists of soluble gel-forming mucins such as MUC2 and MUC5A that are secreted by Goblet cells, IgA antibodies, host defense peptides, and other anti-microbial components [ 1 ]. Another component of the mucus layer are transmembrane mucins, which are large glycoproteins that are expressed on the apical surface of enterocytes and Goblet cells.
Transmembrane mucins have a highly glycosylated extracellular domain with potential barrier function, a transmembrane domain and a cytoplasmic tail that links to signaling pathways [ 3 ]. MUC1 is the most extensively studied transmembrane mucin and is highly expressed at mucosal surfaces including the stomach and the intestinal tract [ 45 ].