口腔细菌感染与多种全身性疾病息息相关，严重威胁着人类健康，药物管控是预防和治疗口腔细菌感染性疾病的重要组成部分。然而，药物的不良反应以及常用抗生素引发的口腔耐药菌的出现，使得新型抗生素的开发变得十分迫切。硫肽类抗生素是来源于微生物、作用机制新颖、毒性低、兼具良好抗感染活性的天然产物类群，对临床多种耐药菌株都有显著的抗菌活性。因此本项目申请团队拟在前期研究的基础上进一步探索其对常见口腔致病菌的生理活性，并通过合成生物学手段对活性突出的硫肽类抗生素进行衍生，在丰富硫肽家族结构多样性的前提下优化其对口腔致病菌的抗菌活性。同时，我们还将结合药物制剂学技术，发展具有口腔粘附特性和缓释特点的原位凝胶，来维持硫肽类抗生素的有效抗菌浓度，以期发展新颖的预防和治疗口腔细菌感染性疾病的临床药物，为口腔临床医学提供新的视野与思路。

Oral bacterial infection is an etiological factor to a variety of systemic diseases which threaten people’s health. Administration of antibiotics is critical in preventing, treating, and curing the infections. However, serious adverse reactions and the emergence of drug-resistant bacteria caused by antibiotics overuse have led to the urgent need of developing new antibiotics. Thiopeptide antibiotics are peptide natural products isolated from microorganisms with novel antibacterial mechanism, low toxicity and excellent anti-infective activity. Previous studies have demonstrated that thiopeptide antibiotics exhibit extraordinary antibacterial-activity against a number of drug-resistant strains clinically. In this study, we intend to further explore their physiological activity against common oral pathogens, perform derivatization of active thiopeptide antibiotics by synthetic biological means, and optimize antibacterial activity against oral pathogens on the premise of enriching the structural diversity of the thiopeptide family. In addition, by taking advantage of pharmaceutics, we aim to develop in-situ gels with oral adhesion and sustained release to maintain the effective antimicrobial concentration of thiopeptide antibiotics. In short, we are developing thiopeptide-derived novel antibiotics for the prevention and treatment of oral bacterial infection, which will shed a new light on clinical stomatology.