Dynamics, cariogenicity, and geographic distribution of Streptococcus mutans adhesin types suggest adaptation to individual hosts

Abstract

Dental caries, the most common chronic infectious disease, involve Streptococcus mutans SpaP A/B/C and Cnm/Cbm adhesin types of different virulence. We have explored their stability and dynamics over 5 years, their geographic distribution, as well as the potentially increased cariogenicity of specific SpaP B subtypes. We performed qPCR and TaqMan typing using whole saliva and isolates from 452 Swedish adolescents followed from 12 to 17 years of age. Approximately 50% of the children were infected at baseline with a single dominant (44%) or mixed (6%) SpaP A, B, or C type, some of which were also Cnm (6%) or Cbm (1%) positive. Stability (+, +) was high for S. mutans infection (85%) and dominant SpaP A or C (80% and 67%) and Cnm or Cbm (85% and 100%) types, but low for SpaP B (51%) and mixed SpaP A/B/C types (26%). Only five children switched from one SpaP type to another, and none between Cnm and Cbm types. Mixed SpaP A/B/C types were typically lost or changed into dominant types. Moreover, children infected with Cnm (n=26) types were more frequent in the northern (Skellefteå) region (p = 0.0041), and those with Cbm types (n=7) in the southern (Umeå) region. Children infected with SpaP B-2 subtypes had a doubled caries experience (p = 0.009) and 5-year caries increment (p = 0.02) compared to those infected with SpaP A. In conclusion, the stable dominant but instable mixed adhesin types and geographic differentiation of Cnm and Cbm types suggest adaptation of low and high cariogenicity types to specific individuals. Swedish adolescents followed from 12 to 17 years of age [7,11,12]. Accordingly, children infected with S. mutans SpaP B and Cnm adhesin types developed more caries than those infected with SpaP A or C and Cbm types or non-infected children [7]. The Cnm phenotype, which occurs in 6% of adolescents, has been implicated in endocarditis and stroke [13][14][15].Both Cnm and SpaP B, one of the three core genome SpaP A, B, or C adhesin types in S. mutans biotypes A, B, and C, exhibit increased acid tolerance and binding to saliva pattern recognition receptor DMBT1 [7,16,17]. Moreover, sequence typing of 70 caries-free and decayed extreme cases suggested a cluster or subgroup of SpaP B-2 types with increased cariogenicity [7]. However, the high cariogenic nature of SpaP B-2 types remains to be verified in the entire sample of 452 adolescents.S. mutans infects 40-80% of subjects and is transmitted similarly to the oral and gut microbiomes from parent to child [18,19]. Infection by S. mutans is dominated by one or a few phenotypes, such as the SpaP A, B, or C adhesin types [18,19], whereas genotype diversity in oral streptococci increases with extent of sequencing [20]. The S. mutans adhesin types and oral, gut, and other microbiomes colonize their niches in a stable fashion over time, though quantitative fluctuations occur in response to antibiotic treatment, traveling, breast feeding, and unknown factors [7,21-23]. However, whether S. mutans adapts to host receptor repertoires similar to uropathogenic Escherich...