Incisive tools for identifying the good and the bad microbes in the mouth

What is it about?

The delicate balance between the human body and the microorganisms inhabiting it is central to health and disease. This intricate relationship between the host and microbes is particularly critical within the oral cavity, which involves the human oral microbiome, a complex ecosystem of microorganisms. However, the precise impact of numerous host salivary proteins on oral health remains unclear. Shedding light on this matter, we explored the role of one such understudied abundant salivary lectin, the carbohydrate-binding proteins that recognize distinct features within the carbohydrate coats of microbes. This lectin, known as zymogen granule protein 16 B (ZG16B) revealed to have a pivotal role in maintaining a balance in the oral microbiome. We recognized the need for tools to elucidate human lectins' interactions in a complex physiological environment, such as the oral cavity. Thereby, we developed a microbial glycan analysis probe (mGAP) based on ZG16B by conjugating a fluorophore or biotin reporter functionality to the lectin to identify interactions of ZG16B with various binding partners. When subjected to the dental plaque swabs, the ZG16B-mGAPs revealed binding to a limited number of oral bacteria, notably, Streptococcus vestibularis, a commensal bacterium widely present in healthy individuals. The ZG16B-microbe interaction is mediated through specific bacterial cell surface carbohydrate polymers. Moreover, the interaction resulted in slower growth of S. vestibularis, potentially controlling the abundance of the bacteria in the oral cavity. In addition to the interactions with commensal bacteria, ZG16B was found to recruit specific salivary mucin - MUC7, a highly glycosylated abundant protein on S. vestibularis, and induces aggregation of the bacteria. Overall, these findings provide an advancement in understanding the role of ZG16B as a lectin in shaping the compositional balance of the oral microbiome by selectively capturing commensal bacteria and regulating their growth via a mucin-assisted clearance mechanism.

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Photo by __ drz __ on Unsplash

Photo by __ drz __ on Unsplash

Why is it important?

The strategy presented here provides the proof of concept for applying human lectin–based probes to discover host–microbe interactions in complex environments. Based on this foundation, the development of additional mGAPs will likely provide valuable insights into the common features of the human soluble lectins regarding their binding specificities to different microbes or glycoproteins and shaping host–microbe interactions. The study's insights into ZG16B's role as a lectin in the oral microbiome provide a deeper understanding of the complex dynamics that underlie oral health and disease. The remarkable specificity of the ZG16B-mGAP for a small subset of organisms promises to be the foundation for a class of probes with unique glycan-binding specificities for bacterial sugar profiling. Future investigation using the ZG16B-mGAP with a broader set of both healthy and diseased subjects may uncover innovative approaches to maintaining oral health and preventing dysbiosis-associated oral diseases, thereby, holding promising potential for developing targeted therapeutic strategies.

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