title: A lactotransferrin single nucleotide polymorphism demonstrates biological activity that can reduce susceptibility to caries.
abstract: Streptococcus mutans is prominently linked to dental caries. Saliva's influence on caries is incompletely understood. Our goal was to identify a salivary protein with anti-S. mutans activity, characterize its genotype, and determine genotypic variants associated with S. mutans activity and reduced caries. An S. mutans affinity column was used to isolate active moieties from saliva obtained from a subject with minimal caries. The bound and eluted protein was identified as lactotransferrin (LTF) by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis and confirmed by Western blotting with LTF antibody. A single nucleotide polymorphism (SNP) that produced a shift from arginine (R) to lysine (K) at amino acid position 47 in the LTF antimicrobial region (rs: 1126478) killed S. mutans in vitro. Saliva from a subject with moderate caries and with the LTF "wild-type" R form at position 47 had no such activity. A pilot genetic study (n = 30) showed that KK subjects were more likely to have anti-S. mutans activity than RR subjects (P = 0.001; relative risk = 3.6; 95% confidence interval [95% CI] = 1.5 to 11.13). Pretreatment of KK saliva with antibody to LTF reduced S. mutans killing in a dose-dependent manner (P = 0.02). KK subjects were less likely to have caries (P = 0.02). A synthetic 11-mer LTF/K peptide killed S. mutans and other caries-related bacteria, while the LTF/R peptide had no effect (P = 0.01). Our results provide functional evidence that the LTF/K variant results in both anti-S. mutans activity and reduced decay. We suggest that the LTF/K variant can influence oral microbial ecology in general and caries-provoking microbes specifically.
authors: Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA. finedh@umdnj.edu
authors: Daniel H
authors: DH
authors: Fine
authors: Gokce A
authors: GA
authors: Toruner
authors: Kabilan
authors: K
authors: Velliyagounder
authors: Vandana
authors: V
authors: Sampathkumar
authors: Dipti
authors: D
authors: Godboley
authors: David
authors: D
authors: Furgang
mesh_terms: D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000494:pharmacology*; D003731:Dental Caries / Q000235:genetics*; D003733:Dental Caries Susceptibility / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007781:Lactoferrin / Q000235:genetics* / Q000494:pharmacology; D008239:Lysine; D020641:Polymorphism, Single Nucleotide; D012463:Saliva / Q000378:metabolism / Q000382:microbiology; D013295:Streptococcus mutans / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D007781:Lactoferrin; D008239:Lysine