title: d-Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans.
abstract: Part of the d-alanine (d-Ala) metabolic pathway in bacteria involves the conversion of l-alanine to d-Ala by alanine racemase and the formation of d-alanyl-d-alanine by d-alanine-d-alanine ligase, the product of which is involved in cell wall peptidoglycan synthesis. At present, drugs that target the metabolic pathway of d-Ala are already in clinical use - e.g. d-cycloserine (DCS) is used as an antibiotic against Mycobacterium tuberculosis. Streptococcus mutans is the main cariogenic bacterium in the oral cavity. Its d-Ala metabolism-associated enzymes alanine racemase and d-alanine-d-alanine ligase are encoded by the genes smu.1834 and smu.599, respectively, which may be potential targets for inhibitors. In this study, the addition of DCS blocked the d-Ala metabolic pathway in S. mutans, leading to bacterial cell wall defects, significant inhibition of bacterial growth and biofilm formation, and reductions in extracellular polysaccharide production and bacterial adhesion. However, the exogenous addition of d-Ala could reverse the inhibitory effect of DCS. Through the means of drug regulation, our study demonstrated, for the first time, the importance of d-Ala metabolism in the survival and biofilm formation of S. mutans. If the growth of S. mutans can be specifically inhibited by designing drugs that target d-Ala metabolism, then this may serve as a potential new treatment for dental caries.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: W
authors.initials: W
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.|Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: X
authors.initials: X
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.|Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.|Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.|Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.|Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: B
authors.initials: B
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.|Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
mesh_terms: D000409:Alanine / Q000378:metabolism* / Q000494:pharmacology; D000411:Alanine Racemase / Q000235:genetics / Q000378:metabolism; D000963:Antimetabolites / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003523:Cycloserine / Q000494:pharmacology; D003731:Dental Caries / Q000382:microbiology / Q000628:therapy; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D013295:Streptococcus mutans / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*
chemical_list: D000963:Antimetabolites; D010457:Peptidoglycan; D003523:Cycloserine; D000411:Alanine Racemase; D010453:Peptide Synthases; C019638:D-alanylalanine synthetase; D000409:Alanine
keywords: Streptococcus mutans; adhesion; antimicrobial; biofilms; d-alanine metabolism; dental caries