Probiotics that moderate pH and antagonize pathogens to promote oral health

Abstract/SummaryCommensal oral streptococci are the most abundant bacteria in the biofilms that colonize the hard and softtissues of the human oral cavity and many areas of the nasopharynx. These health-associated bacteria employmultiple diverse adhesion strategies and produce a spectrum of compounds and macromolecules that inhibitthe colonization and virulence of pathogens. With support from R01 DE25832, a large collection of commensaloral streptococci has been isolated from healthy subjects, then characterized at the phenotypic and genomiclevels for properties that may promote oral and systemic health. Here, we propose to screen these highlydiverse strains for their ability to bind to and degrade purified SARS-CoV-2 surface proteins and to interferewith CoV-2 Spike protein engagement of the viral receptor, ACE2. Standard methods will then be used toidentify the streptococcal gene products that mediate inhibitory activities. Defined mutants and overexpressingstrains will be utilized to confirm the results. Though not a focus of this Urgent Revision application, it isnoteworthy that, as part of DE25832, we have developed a mouse model in which we can establish variouscommensal streptococci in the oral cavity, then challenge the commensal-colonized mice with a pathogen(s).Such a model could be adapted to in vivo animal challenge studies. Importantly, novel systems for formulationand delivery of one of our commensal strains have already been optimized through an internationalcollaboration, and thus we are well positioned to rapidly translate our in vitro findings to clinical trials of atherapeutic probiotic intervention.