Abstract
High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease.
Highlights
The development of dental caries is a complex process that is primarily dependent on the presence of microbial biofilms, the composition and biochemical activity of the biofilm organisms, and the diet of the host; but is affected by a variety of other factors that include the genetic constitution and behavior of the host, tooth architecture and exposure to fluoride [1,2,3,4,5]
Through genome sequence analysis we were surprised to discover that one of the isolates characterized in this study, Smu77/NV1996 [30], was a genetically-engineered derivative of S. mutans V403 containing insertionally-inactivated gtfBC, gtfD and ftf genes, and represents strain V1996 originally described by Munro et al [47]
S. mutans is a genetically-diverse species that co-exists in the oral cavity with a number of other streptococci and hundreds of additional species of bacteria from a wide range of taxa [90,91]
Summary
The development of dental caries is a complex process that is primarily dependent on the presence of microbial biofilms, the composition and biochemical activity of the biofilm organisms, and the diet of the host; but is affected by a variety of other factors that include the genetic constitution and behavior of the host, tooth architecture and exposure to fluoride [1,2,3,4,5]. Streptococcus mutans has long been acknowledged as the species of bacteria most closely associated with the initiation of dental caries [6,7]. The three key virulence attributes of S. mutans that enable this organism to cause dental caries are the ability to form biofilms on the tooth, mediated by sucrosedependent and sucrose-independent mechanisms [11]; production of organic acids via metabolism of dietary carbohydrates; and the ability to grow and to continue to produce acids in a low pH environment, known as aciduricity [6,12]. The ability of S. mutans to rapidly adapt to environmental stresses appears to be central to its ability to form biofilms, persist in the host, and to compete with other oral bacteria, when conditions are conducive to the development of dental caries [13]. The competence pathway of S. mutans is linked to the production of bacteriocins, which kill susceptible closely related species, eliminating competitors while increasing the genetic material available for homologous recombination [15]
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