A new small molecule inhibits Streptococcus mutans biofilms invitro and in vivo

被引:23
作者
Pan, W. [1 ,2 ]
Fan, M. [1 ,2 ]
Wu, H. [3 ]
Melander, C. [4 ]
Liu, C. [1 ,2 ]
机构
[1] Wuhan Univ, Sch & Hosp Stomatol, State Key Lab Breeding Base Basic Sci Stomatol Hu, Wuhan 430079, Peoples R China
[2] Wuhan Univ, Sch & Hosp Stomatol, Key Lab Oral Biomed Engn, Minist Educ, Wuhan 430079, Peoples R China
[3] UAB, Sch Dent, Dept Pediat Dent, Birmingham, AL USA
[4] N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA
关键词
antimicrobials; biofilm; dental caries; small molecule; Streptococci; ACINETOBACTER-BAUMANNII; CYTOTOXICITY; BACTERIAL; TOXICITY; GORDONII; EXTRACT; ANALOGS; CARIES; GENES; CELLS;
D O I
10.1111/jam.12940
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
AimsThe aim of this study was to identify new small molecules that can inhibit Streptococcus mutans biofilms by invitro and invivo model. Methods and ResultsWe evaluated the effect of a small molecule 2-amino-imidazole/triazole conjugate (2-AI/T) on the formation of Strep.mutans biofilms by culturing in 96-well plates. Toxicity was assessed through cell culture and intragastrically administering to mice. The anti-biofilm and anti-caries effects were investigated invivo. The inhibitive mechanism was detected by isobaric tag for relative and absolute quantification (itraq) and RT-QPCR. In vitro and invivo study revealed that 2-AI/T significantly inhibited biofilm formation of Strep.mutans and is more so than inhibiting planktonic cells without toxicity. The ribosome and histidine metabolism pathways of Strep.mutans were significantly regulated by this compound. ConclusionsThese results suggest that the 2-AI/T conjugate is a potent inhibitor that can be potentially developed into a new drug to treat and prevent dental caries. Significance and Impact of the StudyThis is the first study to use small molecule from marine natural products, to protect from dental caries invivo. It has potential broad range application in clinical caries prevention, or as a bioactive ingredient for food applications.
引用
收藏
页码:1403 / 1411
页数:9
相关论文
共 34 条
  • [1] The antimicrobial effects of deglycyrrhizinated licorice root extract on Streptococcus mutans UA159 in both planktonic and biofilm cultures
    Ahn, Sug-Joon
    Cho, Eun-Jung
    Kim, Hyoung-Jun
    Park, Soon-Nang
    Lim, Yun-Kyong
    Kook, Joong-Ki
    [J]. ANAEROBE, 2012, 18 (06) : 590 - 596
  • [2] Biosynthesis, asymmetric synthesis, and pharmacology, including cellular targets, of the pyrrole-2-aminoimidazole marine alkaloids
    Al-Mourabit, Ali
    Zancanella, Manuel A.
    Tilvi, Supriya
    Romo, Daniel
    [J]. NATURAL PRODUCT REPORTS, 2011, 28 (07) : 1229 - 1260
  • [3] Antibiofilm Activity of a Diverse Oroidin Library Generated through Reductive Acylation
    Ballard, T. Eric
    Richards, Justin J.
    Aquino, Arianexys
    Reed, Catherine S.
    Melander, Christian
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 2009, 74 (04) : 1755 - 1758
  • [4] Acute cytotoxicity testing with cultured human lung and dermal cells
    Barile, FA
    Cardona, M
    [J]. IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL, 1998, 34 (08) : 631 - 635
  • [5] Regulation of the Histidine Utilization (Hut) System in Bacteria
    Bender, Robert A.
    [J]. MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2012, 76 (03) : 565 - 584
  • [6] Proteomic and Functional Analyses Reveal a Unique Lifestyle for Acinetobacter baumannii Biofilms and a Key Role for Histidine Metabolism
    Cabral, Maria P.
    Soares, Nelson C.
    Aranda, Jesus
    Parreira, Jose R.
    Rumbo, Carlos
    Poza, Margarita
    Valle, Jaione
    Calamia, Valentina
    Lasa, Inigo
    Bou, German
    [J]. JOURNAL OF PROTEOME RESEARCH, 2011, 10 (08) : 3399 - 3417
  • [7] Cytotoxicity of the MEIC reference chemicals in rat hepatoma-derived Fa32 cells
    Dierickx, PJ
    [J]. TOXICOLOGY, 2000, 150 (1-3) : 159 - 169
  • [8] Antibacterial effect of parabens against planktonic and biofilm Streptococcus sobrinus
    Doron, S
    Friedman, M
    Falach, M
    Sadovnic, E
    Zvia, H
    [J]. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2001, 18 (06) : 575 - 578
  • [9] A Submarine Journey: The Pyrrole-Imidazole Alkaloids
    Forte, Barbara
    Malgesini, Beatrice
    Piutti, Claudia
    Quartieri, Francesca
    Scolaro, Alessandra
    Papeo, Gianluca
    [J]. MARINE DRUGS, 2009, 7 (04) : 705 - 753
  • [10] Inhibition of Pseudomonas aeruginosa biofilm formation with bromoageliferin analogues
    Huigens, Robert W., III
    Richards, Justin J.
    Parise, Gina
    Ballard, T. Eric
    Zeng, Wei
    Deora, Rajendar
    Melander, Christian
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (22) : 6966 - +