Strategic protein target analysis for developing drugs to stop dental caries.
Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.
Division of Pediatric Dentistry, Department of Orofacial Sciences, University of California, San Francisco, CA, USA. horst@salilab.org
J A
JA
Horst
U
U
Pieper
A
A
Sali
L
L
Zhan
G
G
Chopra
R
R
Samudrala
J D B
JD
Featherstone
D030562:Databases, Protein; D003731:Dental Caries / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D003773:Dental Plaque / Q000382:microbiology*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D040901:Proteomics / Q000379:methods*; D013295:Streptococcus mutans / Q000235:genetics* / Q000648:ultrastructure; D040681:Structural Homology, Protein; D037521:Virulence Factors
D037521:Virulence Factors