Contribution of Streptococcus Pseudopneumoniae and Salivarius to vocal fold mucosal integrity and function

Structural changes to vocal fold (VF) epithelium, namely loosened intercellular junctions have been reported in VF benign lesions. Potential mechanisms responsible for the disruption of cell junctions do not address the contribution of resident microbial communities to this pathological phenomenon. In this study, we focused on determining the relationship between Streptococcus pseudopneumoniae (SP), a dominant bacterial species associated with benign lesions, and S. salivarius (SS), a commensal bacterium, with human VF epithelial cells, in our three-dimensional model of human VF mucosa. This experimental system enabled direct deposition of bacteria onto constructs at the Air/Liquid interface allowing for the assessment of bacteria-host interactions at cellular, molecular and ultrastructural levels. Our findings demonstrate that SP disrupts VF epithelial integrity and initiates inflammation via exported products, HtrA1 and pneumolysin. In contrast, SS attaches to VF epithelium, reduces inflammation and induces Mmp2-mediated apical desquamation of infected cells to mitigate the impact of pathogens. In conclusion, this study highlights the complexity of microbial involvement in VF pathology and potential VF mucosal restoration in the presence of laryngeal commensals.