@article {Hoffman675538, author = {Casandra L Hoffman and Alejandro Aballay}, title = {Host mucin is subverted by Pseudomonas aeruginosa during infection to provide free glycans required for successful colonization}, elocation-id = {675538}, year = {2019}, doi = {10.1101/675538}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The mucosal barrier, found lining epithelial cells, serves multiple functions in a range of animals. The major structural components of mucus are mucins, which are heavily glycosylated proteins that are either membrane bound or secreted by the epithelial cells. Mucins are key components of the innate immune system, as they are involved in the clearance of pathogens from the airways and intestines, and their expression is typically upregulated upon epithelial cell exposure to a variety of pathogens. In this study, we identified the mucin MUL-1 as an innate immune factor that appears to be utilized by P. aeruginosa to colonize hosts. We found that while the expression of several mucins, including MUL-1, increased upon P. aeruginosa infection of the nematode Caenorhabditis elegans, silencing of or deletion of mul-1 resulted in enhanced survival and reduced bacterial accumulation. P. aeruginosa required host sialidase CTSA-1.1 to use mucin-derived glycans to colonize the host, while sialidase-encoding bacteria required host MUL-1 but not CTSA-1.1 to cause a lethal infection. This role of mucins and free glycans in host-pathogen interaction appears to be conserved from C. elegans to humans, as P. aeruginosa binding to human lung epithelial cells was also enhanced in the presence of free glycans, and free glycans reversed the binding defect of P. aeruginosa to human lung cells lacking the mucin MUC1.Author Summary The gastrointestinal, respiratory, reproductive, and urinary tracts, are large surfaces exposed to the exterior environment and thus, these mucosal epithelial tissues serve as primary routes of infection. One of the first lines of defense present at these barriers 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 effectors. In this study, we describe the ability of Pseudomonas aeruginosa to utilize mucin-derived glycans to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also show conserved mechanisms of P. aeruginosa virulence traits, by demonstrating that free glycans alter the ability of the bacteria to bind to human lung alveolar epithelial cells. Over the course of host-pathogen evolution, pathogens seem to have evolved to use mucins for their own advantage, and thus one of the biggest questions is which party benefits from pathogen-mucin binding. By gaining a better understanding of pathogen-mucin interactions, we can better protect against pathogen infection.}, URL = {https://www.biorxiv.org/content/early/2019/06/20/675538}, eprint = {https://www.biorxiv.org/content/early/2019/06/20/675538.full.pdf}, journal = {bioRxiv} }