Cariogenic potential of the Streptococcus mutans Cid/Lrg system: an in vivo animal case study

In our prior study using a dual-species (Streptococcus mutans/Streptococcus gordonii) competitive mouse caries model to investigate the contribution of S. mutans LrgAB to in vivo fitness, S. mutans wild-type and ΔlrgAB mutants consistently outnumbered S. gordonii and had high caries scores, even though the ΔlrgAB mutant is highly sensitive to oxidative stress. To determine whether the highly cariogenic sucrose diet used in the previous study masked the contribution of LrgAB to competitive fitness of S. mutans against S. gordonii, we recapitulated our previous mouse caries experiment with a modification in which 4% sucrose drinking water was replaced with sterile water, hypothesized to decrease the frequency of exposure of mice to sucrose, a determinant in the cariogenicity of S. mutans. Given that both S. mutans ΔlrgAB and ΔcidB mutants are sensitive to oxidative stress and share similar transcriptional profiles, these strains, as well as wild-type UA159, were tested in this modified dual-species mouse caries model. When comparing between groups the colonization within molar dental biofilms of S. mutans strains, ΔlrgAB mutant was at a level similar to the wild type, whereas S. mutans ΔcidB was modestly lower than both wild-type and S. mutans ΔlrgAB. The severity of total sulcal caries in both the ∆cidB and ∆lrgAB mutant infections was significantly lower than that of wild type. These results demonstrate that the Cid/Lrg system aids in S. mutans fitness against S. gordonii and caries potential in vivo, a phenotype likely masked in our previous study by more frequent exposure to sucrose.IMPORTANCEThe development of a mature biofilm on the tooth surface is the central event in the pathogenesis of dental caries, which primarily requires that cariogenic organisms withstand the limited resources or environmental fluctuations experienced in the oral cavity. The sensitive and heterogeneous response of the cid and lrg operons to complex external signals has been hypothesized to trigger differentiation of the Streptococcus mutans biofilm community into distinct functional subpopulations to promote survival and persistence of the S. mutans community when challenged by an unfavorable environment. The study described herein enlightens our understanding of how Cid/Lrg contributes to S. mutans pathogenic potential in vivo (caries development), warranting further research regarding the adaptive role of Cid/Lrg system in human oral biofilms toward the development of anti-caries strategies directed at the Cid/Lrg system.