IRG-2
PI: Katharina Ribbeck
A slimy layer of mucus serves as the first line of defense against problematic microbes like the bacterial pathogen Pseudomonas aeruginosa.
We have identified mucins, the major gel-forming components of mucus, and their complex sugar structures (glycans) as protective molecules that suppress microbial virulence traits including toxin secretion, bacterial communication, and surface attachment.
This virulence reduction is associated with less host cell killing in vitro (Figure) and less colonization of burn wounds.
Significance: By attenuating the virulence of pathogens rather than eradicating them, mucin glycans are attractive candidates for novel therapeutics.
Top: In medium alone, P. aeruginosa (green) attaches to host cells (bright field), triggering cellular rounding and death (red). Bottom: The presence of mucin prevents P. aeruginosa from attaching to and killing host cells, thus maintaining a healthy host cell monolayer without rounded morphology.
Wheeler, K. M., Cárcamo-Oyarce, G., Turner, B. S., Dellos-Nolan, S., Co, J. Y., Lehoux, S., Cummings, R. D., Wozniak, D. J., and Ribbeck, K. “Mucin Glycans Attenuate the Virulence of Pseudomonas Aeruginosa in Infection.” Nature Microbiology, 4(12):2146–2154, 2019. <doi:10.1038/s41564-019-0581-8>