Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host–microbe interactions with oral commensals
Name
ghosh-et-al-2023-human-oral-lectin-zg16b-acts-as-a-cell-wall-polysaccharide-probe-to-decode-host-microbe-interactions.pdf
Description
Published version
Size
2.35 MB
Format
Adobe PDF
Checksum (MD5)
64d6e817f9a1213b41a30f17974ba09c
Author(s)
Ghosh, Soumi
Ahearn, Christian P
Isabella, Christine R
Marando, Victoria M
Dodge, Gregory J
Bartlett, Helen
McPherson, Robert L
Dugan, Amanda E
Jain, Shikha
Neznanova, Lubov
Date Issued
May 30, 2023
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
S. Ghosh,C.P. Ahearn,C.R. Isabella,V.M. Marando,G.J. Dodge,H. Bartlett,R.L. McPherson,A.E. Dugan,S. Jain,L. Neznanova,H. Tettelin,R. Putnik,C.L. Grimes,S. Ruhl,L.L. Kiessling, & B. Imperiali, Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host–microbe interactions with oral commensals, Proc. Natl. Acad. Sci. U.S.A. 120 (22) e2216304120, (2023).
Version
Final published version
Abstract
The oral microbiome is critical to human health and disease, yet the role that host salivary proteins play in maintaining oral health is unclear. A highly expressed gene in human salivary glands encodes the lectin zymogen granule protein 16 homolog B (ZG16B). Despite the abundance of this protein, its interaction partners in the oral microbiome are unknown. ZG16B possesses a lectin fold, but whether it binds carbohydrates is unclear. We postulated that ZG16B would bind microbial glycans to mediate recognition of oral microbes. To this end, we developed a microbial glycan analysis probe (mGAP) strategy based on conjugating the recombinant protein to fluorescent or biotin reporter functionality. Applying the ZG16B-mGAP to dental plaque isolates revealed that ZG16B predominantly binds to a limited set of oral microbes, including Streptococcus mitis, Gemella haemolysans, and, most prominently, Streptococcus vestibularis. S. vestibularis is a commensal bacterium widely distributed in healthy individuals. ZG16B binds to S. vestibularis through the cell wall polysaccharides attached to the peptidoglycan, indicating that the protein is a lectin. ZG16B slows the growth of S. vestibularis with no cytotoxicity, suggesting that it regulates S. vestibularis abundance. The mGAP probes also revealed that ZG16B interacts with the salivary mucin MUC7. Analysis of S. vestibularis and MUC7 with ZG16B using super-resolution microscopy supports ternary complex formation that can promote microbe clustering. Together, our data suggest that ZG16B influences the compositional balance of the oral microbiome by capturing commensal microbes and regulating their growth using a mucin-assisted clearance mechanism.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivatives
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DOI of Published Version
https://doi.org/10.1073/pnas.2216304120
