Mucin Glycans Signal through the Sensor Kinase RetS to Inhibit Virulence-Associated Traits in Pseudomonas aeruginosa
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nihms-1655168.pdf
Description
Accepted version
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2.6 MB
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Author(s)
Wang, Benjamin X
Wheeler, Kelsey M
Cady, Kyle C
Lehoux, Sylvain
Cummings, Richard D
Laub, Michael T
Ribbeck, Katharina
Date Issued
October 2020
Journal
Current Biology
Publisher
Elsevier BV
Citation
Wang, Benjamin X, Wheeler, Kelsey M, Cady, Kyle C, Lehoux, Sylvain, Cummings, Richard D et al. 2021. "Mucin Glycans Signal through the Sensor Kinase RetS to Inhibit Virulence-Associated Traits in Pseudomonas aeruginosa." Current Biology, 31 (1).
Version
Author's final manuscript
Abstract
© 2020 Mucus is a densely populated ecological niche that coats all non-keratinized epithelia, and plays a critical role in protecting the human body from infections. Although traditionally viewed as a physical barrier, emerging evidence suggests that mucus can directly suppress virulence-associated traits in opportunistic pathogens including Pseudomonas aeruginosa. However, the molecular mechanisms by which mucus affords this protection are unclear. Here, we show that mucins, and particularly their associated glycans, signal through the Dismed2 domain of the sensor kinase RetS in P. aeruginosa. We find that this RetS-dependent signaling leads to the direct inhibition of the GacS-GacA two-component system, the activity of which is associated with a chronic infection state. This signaling includes downregulation of the type VI secretion system (T6SS), and prevents T6SS-dependent bacterial killing by P. aeruginosa. Overall, these results shed light on how mucus impacts P. aeruginosa behavior, and may inspire novel approaches for controlling P. aeruginosa infections.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Biological Engineering
Howard Hughes Medical Institute
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CUB.2020.09.088
