Abstract
The human oral microbiome consists of diverse microbes actively communicating and interacting through a variety of biochemical mechanisms. Dental caries is a major public health issue caused by fermentable carbohydrate consumption that leads to dysbiosis of the oral microbiome. Streptococcus mutans is a known major contributor to caries pathogenesis, due to its exceptional ability to form biofilms in the presence of sucrose, as well as to its acidophilic lifestyle. S. mutans can also kill competing bacteria, which are typically health associated, through the production of bacteriocins and other small molecules. A subset of S. mutans strains encode the muc biosynthetic gene cluster (BGC), which was recently shown to produce the tetramic acids, mutanocyclin and reutericyclins A, B, and C. Reutericyclin A displayed strong antimicrobial activity and mutanocyclin appeared to be anti-inflammatory; however the effect of these compounds, and the carriage of muc by S. mutans, on the ecology of the oral microbiota is not known, and was examined here using a previously developed in vitro biofilm model derived from human saliva. While reutericyclin significantly inhibited in vitro biofilm formation and acid production at sub-nanomolar concentrations, mutanocyclin did not present any activity until the high micromolar range. 16S rRNA gene sequencing revealed that reutericyclin drastically altered the biofilm community composition, while mutanocyclin showed a more specific effect, reducing the relative abundance of cariogenic Limosilactobacillus fermentum. Mutanocyclin or reutericyclin produced by the S. mutans strains amended to the community did not appear to affect the community in the same way as the purified compounds, although the results were somewhat confounded by the differing growth rates of the S. mutans strains. Regardless of the strain added, the addition of S. mutans to the in vitro community significantly increased the abundance of S. mutans and Veillonella infantium, only. Overall, this study illustrates that reutericyclin A and mutanocyclin do impact the ecology of a complex in vitro oral biofilm; however, further research is needed to determine the extent to which the production of these compounds affects the virulence of S. mutans.
Highlights
The oral microbiota contains a metabolically dynamic community of bacteria, ranging from health-associated commensals, to opportunistic pathogens and overtly pathogenic taxa [1,2,3]
Previous studies identified that a subset of S. mutans strains (22 of the 169 strains examined by Liu et al.) encoded a biosynthetic gene cluster (BGC) that was highly homologous to the reutericyclin BGC, which was originally identified in the genomes of Lactobacillus reuteri [13,14,15,16]
Purified reutericyclin was purchased from MedChemExpress (Monmouth Junction, NJ, USA), and mutanocyclin was synthesized from D-leucine ethyl ester hydrochloride and 2, 2, 6-trimethyl-4H-1, 3-dioxin4-one and purified as described previously [16]
Summary
The oral microbiota contains a metabolically dynamic community of bacteria, ranging from health-associated commensals, to opportunistic pathogens and overtly pathogenic taxa [1,2,3]. Reutericyclin (produced by S. mutans B04Sm5) inhibited the growth of neighboring commensal streptococci, its role in a broader ecology of the complex oral microbiota was not known [16]. It is unclear if the carriage of muc affects S. mutans pathogenicity in caries-associated dysbiosis. The effects on oral biofilm growth, bacterial taxonomic diversity, and community gene transcription activities, were examined by the introduction of reutericyclin A, mutanocyclin, and S. mutans strains which produce one, both, or neither of these compounds into a complex in vitro biofilm model derived from human saliva [20, 21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
