Your mouth is an important interface between the outside world and the inside of your body. Everything you breathe, chew, or drink interacts with your oral cavity—proteins and microbes, including microbes that harm us. When things go wrong, the results can range from mild, like bad breath, to severe, like tooth and gum decay, to more severe effects on the intestines and other parts of the body.
Although the oral microbiome plays a critical role as a front-line defense for human health and disease, we still know little about the intricacies of host-microbe interactions in complex physiological around the mouth; a better understanding of these interactions is key to developing treatments for human disease.
In a recent study published in PNAS, a team of scientists from MIT and elsewhere revealed that one of the most abundant proteins found in our saliva binds to the surface of select microbes found in the mouth. The findings shed light on how salivary proteins and mucus play a role in maintaining the oral cavity microbiome.
The collaboration includes members of the labs of Barbara Imperiali of the MIT Department of Biology and Laura Kiessling of the MIT Department of Chemistry, as well as the groups of Stefan Ruhl of the University at Buffalo School of Dental Medicine and Catherine Grimes of the University of Delaware.
The work focused on an abundant oral cavity protein called zymogen granule protein 16 homolog B (ZG16B). Finding the interaction partners of ZG16B and gaining insight into its function are the main goals of the project. To do this, Soumi Ghosh, a postdoc in the Imperiali lab, and colleagues engineered ZG16B to add reporter tags such as fluorophores. They call these modified proteins “microbial glycan analysis probes (mGAPs)” because they allow them to identify the binding partners of ZG16B using complementary methods. They applied analyzes to samples of the healthy oral microbiome to identify target microbes and binding partners.
The results excited them.
“ZG16B doesn’t just bind to random bacteria. It’s very focused on certain species, including a commensal bacteria called Streptococcus vestibularis,” said Ghosh, who is the first author of the paper.
Commensal bacteria are found in a normal healthy microbiome and do not cause disease.
Using mGAPs, the team showed that ZG16B binds to cell wall polysaccharides in bacteria, indicating that ZG16B is a lectin, a carbohydrate-binding protein. In general, lectins are responsible for cell-cell interactions, signaling pathways, and some innate immune responses against pathogens. “This is the first time it has been experimentally proven that ZG16B acts as a lectin because it binds to carbohydrates on the cell surface or cell wall of bacteria,” Ghosh emphasized.
ZG16B has also been shown to recruit Mucin 7 (MUC7), a salivary glycoprotein in the oral cavity, and the results suggest that ZG16B helps maintain a healthy balance in the oral microbiome by forming a complex with MUC7 and some bacteria. The results show that ZG16B regulates bacterial abundance by preventing overgrowth through agglutination when bacteria exceed a certain growth threshold.
“ZG16B therefore, seems to act as a missing link in the system; it binds to different types of glycans – the microbial glycans and the mucin glycans – and ultimately, maintains a healthy balance in our oral cavity,” says Ghosh.
Further work on this analysis and oral microbiome samples from healthy and diseased subjects may also reveal the importance of lectins for oral health and disease.
Current attention is focused on the development and use of additional mGAPs based on other human lectins, such as those found in serum, liver, and intestine to reveal their specific binding and their roles in host-microbe interactions.
“The research produced in this collaboration shows the kind of synergy that made me excited to move to MIT five years ago,” Kiessling said. “I have worked with great scientists who share my interest in chemistry and the biology of carbohydrates.”
Kiessling and Imperiali, both senior authors of the paper, coined the term for the analyzes they conducted: “mGAPS to fill the gaps” in our understanding of the role of lectins in the human microbiome, according to said Ghosh.
“If we want to develop therapeutics against bacterial infection, we need a better understanding of host-microbe interactions,” says Ghosh. “The importance of our study is to prove that we can make very good tests for microbial glycans, determine their importance in the front-line defense of the immune system, and, finally, develop a therapeutic approach to the disease.”
Soumi Ghosh et al, Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host-microbe interactions in oral commensals, Proceedings of the National Academy of Sciences (2023). DOI: 10.1073/pnas.2216304120
Provided by the Massachusetts Institute of Technology
This story is republished courtesy of MIT News (web.mit.edu/newsoffice/), a popular site that covers news about research, innovation and teaching at MIT.
Citation: Probe expands understanding of oral cavity homeostasis (2023, July 18) retrieved on July 18, 2023 from https://phys.org/news/2023-07-probe-oral-cavity-homeostasis.html
This document is subject to copyright. Except for any fair dealing for the purpose of private study or research, no part may be reproduced without written permission. Content is provided for informational purposes only.