title: Betulin inhibits cariogenic properties of Streptococcus mutans by targeting vicRK and gtf genes.
abstract: Streptococcus mutans, a multivirulent pathogen is considered the primary etiological agent in dental caries. Development of antibiotic resistance in the pathogen has created a need for novel antagonistic agents which can control the virulence of the organism and reduce resistance development. The present study demonstrates the in vitro anti-virulence potential of betulin (lup-20(29)-ene-3β,28-diol), an abundantly available plant triterpenoid against S. mutans UA159. Betulin exhibited significant dose dependent antibiofilm activity without affecting bacterial viability. At 240 µg/ml (biofilm inhibitory concentration), betulin inhibited biofilm formation and adherence to smooth glass surfaces by 93 and 71 % respectively. It reduced water insoluble glucan synthesis by 89 %, in conjunction with down regulation of gtfBC genes. Microscopic analysis confirmed the disruption in biofilm architecture and decreased exopolysaccharide production. Acidogenicity and aciduricity, key virulence factors responsible for carious lesions, were also notably affected. The induced auto-aggregation of cells upon treatment could be due to the down regulation of vicK. Results of gene expression analysis demonstrated significant down-regulation of virulence genes upon betulin treatment. Furthermore, the nontoxic effect of betulin on peripheral blood mononuclear cells even after 72 h treatment makes it a strong candidate for assessing its suitability to be used as a therapeutic agent.
authors.affiliation: Department of Biotechnology, Alagappa University, II Floor, Science Campus, Karaikudi, Tamil Nadu, 630 004, India.
authors.forename: Dharmaprakash
authors.initials: D
authors.lastname: Viszwapriya
authors.affiliation: Department of Biotechnology, Alagappa University, II Floor, Science Campus, Karaikudi, Tamil Nadu, 630 004, India.
authors.forename: Ganapathy Ashwinkumar
authors.initials: GA
authors.lastname: Subramenium
authors.affiliation: Department of Biotechnology, Alagappa University, II Floor, Science Campus, Karaikudi, Tamil Nadu, 630 004, India.
authors.forename: Solai
authors.initials: S
authors.lastname: Radhika
authors.affiliation: Department of Biotechnology, Alagappa University, II Floor, Science Campus, Karaikudi, Tamil Nadu, 630 004, India. sk_pandian@rediffmail.com.
authors.forename: Shunmugiah Karutha
authors.initials: SK
authors.lastname: Pandian
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003731:Dental Caries / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D013295:Streptococcus mutans / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D000094062:Betulinic Acid
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D014315:Triterpenes; D037521:Virulence Factors; C002503:betulin; D000094062:Betulinic Acid
keywords: Anti-cariogenic; Betulin; Biofilm; Glucan; Streptococcus mutans; VicRK