Host Mucin Is Exploited by Pseudomonas aeruginosa To Provide Monosaccharides Required for a Successful Infection.

One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides -acetyl-galactosamine and -acetylglucosamine are required for killing of We also found that the defective adhesion of to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides. One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of to colonize the intestine and ultimately cause death in We also demonstrate that monosaccharides alter the ability of bacteria to bind to both intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.