Additive attenuation of virulence and cariogenic potential of Streptococcus mutans by simultaneous inactivation of the ComCDE quorum-sensing system and HK/RR11 two-component regulatory system

Department of Applied Oral Sciences, Dalhousie University, Halifax, NS, Canada.
Microbiology (Impact Factor: 2.56). 12/2008; 154(Pt 11):3256-65. DOI: 10.1099/mic.0.2008/019455-0
Source: PubMed


The genome of Streptococcus mutans harbours 13 two-component signal transduction systems (TCSTSs). Of these, a peptide-mediated quorum-sensing system, ComCDE, and the HK/RR11 two-component system are well known to regulate several virulence-associated traits in in vitro experiments, including genetic competence, bacteriocin production, biofilm formation and stress responses. In this study, we investigated the hypothesis that inactivation of ComCDE, HK/RR11 or both systems would attenuate the virulence and cariogenicity of S. mutans. The results showed that simultaneous inactivation of both signal transduction systems additively attenuated S. mutans virulence and cariogenicity, since inactivation of either of these systems alone did not result in the same degree of effect. The double deletion mutant SMcde-hk11 was defective in genetic competence, had a reduced acid production, was unable to grow at pH 5.0 and formed an abnormal biofilm with reduced biomass. Animal studies showed that this mutant had reduced capabilities for oral colonization, succession and initiation of dental caries. A competitive index (CI) analysis using a mixed-infection animal model revealed that all the mutants, particularly SMcde-hk11, had reduced fitness in their ecological niches and were unable to compete with the wild-type strain for persistence in dental biofilms. The evidence from this study suggests that the ComCDE and HK/RR11 signal transduction systems can be considered to be novel targets for the development of strategies in the prevention and treatment of S. mutans infections.

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    • "By regulating a set of stress-related genes, streptococci can overcome harsh environments and enhance their chances for survival (Ibrahim et al., 2004; Suntharalingam et al., 2009; Downey et al., 2014). Moreover, next genome sequencing analysis has indicated that the species S. pyogenes and S. mutans have 13 putative TCSs (Li et al., 2008; Hertzén et al., 2012), whereas S. agalactiae contain up to 21 TCSs (Vasilyeva et al., 2015). "
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    • "Streptococcus mutans is another good example of bacteria that use quorum sensing to regulate social activity, biofilm formation and virulence [14,48–51]. S. mutans is a bacterium that has adapted a biofilm life-style for survival and persistence in its natural ecosystem, dental plaque [19,48]. "
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    • "In this context, the maintenance of balance in the oral microbiota is also important because many oral microorganisms possess beneficial properties and are associated with health (Marsh, 1991). Besides using antimicrobial agents to control cariogenic bacteria, suppressing their mechanisms of virulence could also be an interesting and promising approach since it would not cause profound alterations in the oral microbiota (Li et al., 2008; Nascimento et al., 2008). Chlorhexidine, triclosan, thymol, and cetylpyridinium chloride have been used as oral antiseptics in cariology (Bouwsma, 1996; Paraskevas, 2005). "
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