Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host-microbe interactions with oral commensals.
Human oral lectin ZG16B acts as a cell wall polysaccharide probe to decode host-microbe interactions with oral commensals.
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DOI：
10.1073/pnas.2216304120
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发表时间：
2023-05-30
影响因子：
11.1
通讯作者：
Imperiali, Barbara
中科院分区：
文献类型：
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作者：
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;Tettelin, Herve;Putnik, Rachel;Grimes, Catherine L.;Ruhl, Stefan;Kiessling, Laura L.;Imperiali, Barbara
关键词：
对于揭示人类凝集素在复杂生理环境（如口腔）中调节宿主-微生物相互作用的作用的策略的需求尚未得到满足。我们从一种主要的口腔凝集素酶原颗粒蛋白16B （ZG16B）中开发了一种微生物聚糖分析探针（mGAP），并应用该探针来研究ZG16B的相互作用。ZG16B通过细胞表面糖缀合物与包括前庭链球菌在内的共生细菌结合并调节其生长。ZG16B还募集唾液黏液蛋白MUC7，诱导前庭链球菌聚集。我们的研究结果表明，ZG16B通过捕获选择性共生菌并通过黏液辅助清除机制防止过度生长，从而帮助维持口腔微生物组的稳态。口腔微生物组对人类健康和疾病至关重要，但宿主唾液蛋白在维持口腔健康中所起的作用尚不清楚。人类唾液腺中有一个高表达的基因编码凝集素酶原颗粒蛋白16同源物B （ZG16B）。尽管这种蛋白质含量丰富，但其在口腔微生物组中的相互作用伙伴尚不清楚。ZG16B具有凝集素折叠，但它是否与碳水化合物结合尚不清楚。我们假设ZG16B可以结合微生物聚糖介导口腔微生物的识别。为此，我们开发了一种基于重组蛋白与荧光或生物素报告功能结合的微生物聚糖分析探针（mGAP）策略。将ZG16B- mgap应用于牙菌斑分离物表明，ZG16B主要与有限的口腔微生物结合，包括炎链球菌、溶血性链球菌和最显著的前庭链球菌。前庭葡萄球菌是一种广泛分布于健康人体内的共生菌。ZG16B通过附着在前庭葡萄球菌肽聚糖上的细胞壁多糖与之结合，表明该蛋白是一种凝集素。ZG16B抑制了前庭葡萄球菌的生长，但无细胞毒性，提示其调节了前庭葡萄球菌的丰度。mGAP探针还发现ZG16B与唾液黏液蛋白MUC7相互作用。ZG16B超分辨显微镜分析前庭S. vestibularis和MUC7支持三元配合物的形成，可以促进微生物聚集。总之，我们的数据表明，ZG16B通过捕获共生微生物并利用黏液辅助清除机制调节其生长，从而影响口腔微生物组的组成平衡。
There is an unmet need for strategies that uncover the roles of human lectins in modulating host–microbe interactions in complex physiological environments such as the mouth. We have developed a microbial glycan analysis probe (mGAP) from a predominant oral cavity lectin zymogen granule protein 16B (ZG16B) and applied the probe to interrogate the interactions of ZG16B. ZG16B binds to commensal bacteria including Streptococcus vestibularis through cell surface glycoconjugates and regulates its growth. ZG16B also recruits the salivary mucin MUC7 and induces the aggregation of S. vestibularis. Our findings suggest that ZG16B assists in maintaining homeostasis in the oral microbiome by capturing selective commensal bacteria and preventing overgrowth by a mucin-assisted clearance mechanism. 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.
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预防宿主防御和疾病的唾液粘蛋白。
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Walker, Suzanne