Kaur Gurmeet, Balamurugan P, Uma Maheswari C, Anitha A, Princy S Adline
Quorum Sensing Laboratory, Centre for Research in Infectious Diseases, School of Chemical and Biotechnology, SASTRA University Thanjavur, India.
Organic Synthesis Group, Department of Chemistry, School of Chemical and Biotechnology, SASTRA University Thanjavur, India.
Front Microbiol. 2016 Jun 6;7:861. doi: 10.3389/fmicb.2016.00861. eCollection 2016.
Dental caries occur as a result of disequilibrium between acid producing pathogenic bacteria and alkali generating commensal bacteria within a dental biofilm (dental plaque). Streptococcus mutans has been reported as a primary cariogenic pathogen associated with dental caries. Emergence of multidrug resistant as well as fluoride resistant strains of S. mutans due to over use of various antibiotics are a rising problem and prompted the researchers worldwide to search for alternative therapies. In this perspective, the present study was aimed to screen selective inhibitors against ComA, a bacteriocin associated ABC transporter, involved in the quorum sensing of S. mutans. In light of our present in silico findings, 1,3-disubstituted urea derivatives which had better affinity to ComA were chemically synthesized in the present study for in vitro evaluation of S. mutans biofilm inhibition. The results revealed that 1,3-disubstituted urea derivatives showed good biofilm inhibition. In addition, synthesized compounds exhibited potent synergy with a very low concentration of fluoride (31.25-62.5 ppm) in inhibiting the biofilm formation of S. mutans without affecting the bacterial growth. Further, the results were supported by confocal laser scanning microscopy. On the whole, from our experimental results we conclude that the combinatorial application of fluoride and disubstituted ureas has a potential synergistic effect which has a promising approach in combating multidrug resistant and fluoride resistant S. mutans in dental caries management.
龋齿是由牙菌斑中产生酸的致病细菌与产生碱的共生细菌之间的失衡所致。变形链球菌被报道为与龋齿相关的主要致龋病原体。由于各种抗生素的过度使用，出现了对多种药物耐药以及对氟耐药的变形链球菌菌株，这一问题日益严重，促使全球的研究人员寻找替代疗法。从这个角度来看，本研究旨在筛选针对ComA的选择性抑制剂，ComA是一种与细菌素相关的ABC转运蛋白，参与变形链球菌的群体感应。根据我们目前的计算机模拟研究结果，本研究化学合成了对ComA具有更好亲和力的1,3 - 二取代脲衍生物，用于体外评估其对变形链球菌生物膜的抑制作用。结果表明，1,3 - 二取代脲衍生物表现出良好的生物膜抑制作用。此外，合成的化合物在抑制变形链球菌生物膜形成方面与极低浓度的氟（31.25 - 62.5 ppm）表现出强大的协同作用，且不影响细菌生长。此外，共聚焦激光扫描显微镜的结果支持了上述结果。总体而言，从我们的实验结果可以得出结论，氟化物和二取代脲的联合应用具有潜在的协同效应，在龋齿管理中对抗耐多药和耐氟的变形链球菌方面具有广阔的应用前景。
