Nitrite Triggers Reprogramming of the Oral Polymicrobial Metabolome by a Commensal Streptococcus

Abstract

Commensal streptococci regulate health and homeostasis within oral polymicrobial communities. Remarkably, high salivary nitrite concentrations have also been associated with improved health in the oral cavity. We previously demonstrated that nitrite assists hydrogen peroxide-producing oral commensal streptococci in regulating homeostasis via the generation of reactive nitrogen species (RNS), which have antimicrobial activity on oral pathogens. However, it is unknown how nitrite and commensal streptococci work in concert to influence the metabolome of oral polymicrobial communities. In this study, we report that nitrite aids commensal streptococci in the inhibition of multi-kingdom pathogens that reside in distinct oral niches, which supports commensal dominance. More importantly, we show that commensal streptococci utilize nitrite to drive the metabolic signature of multispecies biofilms in a manner that supports commensal metabolism and resistance to RNS, and restricts metabolic processes that are required for pathogen virulence. Taken together, our study provides insight into how commensal streptococci use nitrite to trigger shifts in the oral polymicrobial metabolome to support health and homeostasis.

Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of Streptococcus mutans

“…Although the mechanisms of such adhesions and coaggregations are not fully elucidated, it is believed that the extracellular polysaccharide (EPS) matrix of S. mutans has an important role in this process. , It is reported that glucans synthesized by Gtfs when incorporated into the tooth pellicle to provide enhanced binding sites for other microorganisms to form stable and persistent microcolonies, which provides mechanical stability to the EPS matrix. , Therefore, Gtf inhibition assays were performed to assess the ability of HA5 to inhibit Gtfs and glucan production using a reported procedure and the IC 50 value was calculated . Compound HA5 exhibited dose-dependent inhibition of glucan production by Gtfs with an IC 50 value of 10.56 μM (Figure B).…”

Aspects of oral streptococcal metabolic diversity: Imagining the landscape beneath the fog

“…Accompanying metabolomic analysis uncovered the secondary metabolite thioproline as a potential protective antioxidant produced S. parasanguinis (Huffines et al, 2022).…”

“…This along with the multicellular spreading behavior of the cross-kingdom biofilm is beneficial to S. mutans survival and biofilm development. The inhibitory effect is heightened by the presence of salivary nitrite (Huffines et al, 2022), which promotes the generation of reactive nitrogen species to which cariogenic species are sensitive.…”

“…The inhibitory effect is heightened by the presence of salivary nitrite (Huffines et al, 2022), which promotes the generation of reactive nitrogen species to which cariogenic species are sensitive. Accompanying metabolomic analysis uncovered the secondary metabolite thioproline as a potential protective antioxidant produced S. parasanguinis (Huffines et al, 2022).…”

“…Inhibition of S. mutans – C. albicans biofilm development is dependent in part on the H 2 O 2 produced by the commensal and is characterized by reduced Gtf activity and sucrose consumption by S. mutans and C. albicans . The inhibitory effect is heightened by the presence of salivary nitrite (Huffines et al, 2022), which promotes the generation of reactive nitrogen species to which cariogenic species are sensitive. Accompanying metabolomic analysis uncovered the secondary metabolite thioproline as a potential protective antioxidant produced S. parasanguinis (Huffines et al, 2022).…”