d-Alanine metabolism is essential for growth and biofilm formation of Streptococcus mutans

被引:42
作者
Qiu, W. [1 ]
Zheng, X. [1 ,2 ]
Wei, Y. [1 ,2 ]
Zhou, X. [1 ,2 ]
Zhang, K. [1 ]
Wang, S. [1 ,2 ]
Cheng, L. [1 ,2 ]
Li, Y. [1 ]
Ren, B. [1 ]
Xu, X. [1 ,2 ]
Li, Y. [1 ]
Li, M. [1 ]
机构
[1] Sichuan Univ, State Key Lab Oral Dis, Chengdu, Peoples R China
[2] Sichuan Univ, West China Hosp Stomatol, Dept Operat Dent & Endodont, Chengdu, Peoples R China
基金
中国国家自然科学基金;
关键词
adhesion; d-alanine metabolism; antimicrobial; biofilms; dental caries; Streptococcus mutans; ALANYL-D-ALANINE; MYCOBACTERIUM-SMEGMATIS; CARIES PROCESS; D-CYCLOSERINE; LIGASE; RACEMASE; CRYSTALLIZATION; ANTIBACTERIAL; MECHANISM; NICOTINE;
D O I
10.1111/omi.12146
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
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.
引用
收藏
页码:435 / 444
页数:10
相关论文
共 35 条
[1]   Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen [J].
Ajdic, D ;
McShan, WM ;
McLaughlin, RE ;
Savic, G ;
Chang, J ;
Carson, MB ;
Primeaux, C ;
Tian, RY ;
Kenton, S ;
Jia, HG ;
Lin, SP ;
Qian, YD ;
Li, SL ;
Zhu, H ;
Najar, F ;
Lai, HS ;
White, J ;
Roe, BA ;
Ferretti, JJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) :14434-14439
[2]   Crystallization and preliminary X-ray analysis of a d-alanyl-d-alanine ligase (EcDdlB) from Escherichia coli [J].
Batson, Sarah ;
Rea, Dean ;
Fulop, Vilmos ;
Roper, David I. .
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 2010, 66 :405-408
[3]   The complex oral microflora of high-risk individuals and groups and its role in the caries process [J].
Beighton, D .
COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, 2005, 33 (04) :248-255
[4]   Effects of mutating putative two-component systems on biofilm formation by Streptococcus mutans UA159 [J].
Bhagwat, SP ;
Nary, J ;
Burne, RA .
FEMS MICROBIOLOGY LETTERS, 2001, 205 (02) :225-230
[5]   Biology of Streptococcus mutans-Derived Glucosyltransferases: Role in Extracellular Matrix Formation of Cariogenic Biofilms [J].
Bowen, W. H. ;
Koo, H. .
CARIES RESEARCH, 2011, 45 (01) :69-86
[6]   Impairment of D-alanine biosynthesis in Mycobacterium smegmatis determines decreased intracellular survival in human macrophages [J].
Chacon, Ofelia ;
Bermudez, Luiz E. ;
Zinniel, Denise K. ;
Chahal, Harpreet K. ;
Fenton, Robert J. ;
Feng, Zhengyu ;
Hanford, Kathy ;
Adams, L. Garry ;
Barletta, Raul G. .
MICROBIOLOGY-SGM, 2009, 155 :1440-1450
[7]   Microbial risk indicators of early childhood caries [J].
Corby, PM ;
Lyons-Weiler, J ;
Bretz, WA ;
Hart, TC ;
Aas, JA ;
Boumenna, T ;
Goss, J ;
Corby, AL ;
Junior, HM ;
Weyant, RJ ;
Paster, BJ .
JOURNAL OF CLINICAL MICROBIOLOGY, 2005, 43 (11) :5753-5759
[8]   Targeted killing of Streptococcus mutans by a pheromone-guided "smart" antimicrobial peptide [J].
Eckert, Randal ;
He, Jian ;
Yarbrough, Daniel K. ;
Qi, Fengxia ;
Anderson, Maxwell H. ;
Shi, Wenyuan .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2006, 50 (11) :3651-3657
[9]   Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions [J].
Fischer, Carol L. ;
Walters, Katherine S. ;
Drake, David R. ;
Dawson, Deborah V. ;
Blanchette, Derek R. ;
Brogden, Kim A. ;
Wertz, Philip W. .
INTERNATIONAL JOURNAL OF ORAL SCIENCE, 2013, 5 (03) :130-140
[10]   Metabolomics Analysis Identifies D-Alanine-D-Alanine Ligase as the Primary Lethal Target of D-Cycloserine in Mycobacteria [J].
Halouska, Steven ;
Fenton, Robert J. ;
Zinniel, Denise K. ;
Marshall, Darrell D. ;
Barletta, Raul G. ;
Powers, Robert .
JOURNAL OF PROTEOME RESEARCH, 2014, 13 (02) :1065-1076