Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 4, Pages 726-731Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1713539115
Keywords
mucus; mucin; Xenopus tropicalis; Aeromonas hydrophila; innate defense
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Funding
- Biotechnology and Biological Sciences Research Council [BB/M021688/1]
- Wellcome Trust [203128/Z/16/Z]
- Biotechnology and Biological Sciences Research Council [BB/M021688/1] Funding Source: researchfish
- Medical Research Council [1342605] Funding Source: researchfish
- BBSRC [BB/M021688/1] Funding Source: UKRI
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Mucosal surfaces represent critical routes for entry and exit of pathogens. As such, animals have evolved strategies to combat infection at these sites, in particular the production of mucus to prevent attachment and to promote subsequent movement of the mucus/microbe away from the underlying epithelial surface. Using biochemical, biophysical, and infection studies, we have investigated the host protective properties of the skin mucus barrier of the Xenopus tropicalis tadpole. Specifically, we have characterized the major structural component of the barrier and shown that it is a mucin glycoprotein (Otogelin-like or Otogl) with similar sequence, domain organization, and structural properties to human gel-forming mucins. This mucin forms the structural basis of a surface barrier (similar to 6 mu m thick), which is depleted through knockdown of Otogl. Crucially, Otogl knockdown leads to susceptibility to infection by the opportunistic pathogen Aeromonas hydrophila. To more accurately reflect its structure, tissue localization, and function, we have renamed Otogl as Xenopus Skin Mucin, or MucXS. Our findings characterize an accessible and tractable model system to define mucus barrier function and host-microbe interactions.
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