Streptococcus mutans, a dental caries causing odontopathogen, produces X-prolyl dipeptidyl peptidase (Sm-XPDAP, encoded by pepX), a serine protease known to have a nutritional role. Considering the potential of proteases as therapeutic targets in pathogens, this study was primarily aimed at investigating the role of Sm-XPDAP in contributing to virulence-related traits. Dipeptidyl peptidase (DPP IV), an XPDAP analogous enzyme found in mammalian tissues,is a well known therapeutic target in Type II diabetes. Based on the hypothesis that gliptins, commonly used as anti-human-DPP IV drugs, may affect bacterial growth upon inhibition of Sm-XPDAP, we have determined their ex vivo antimicrobial and anti-biofilm activity towards S. mutans. All three DPP IV drugs tested reduced biofilm formation as determined by crystal violet staining. To link the observed biofilm inhibition to the human-DPP IV analogue present in S. mutans UA159, a pepX isogenic mutant was generated. In addition to reduced biofilm formation, CLSM studies of the biofilm formed by the pepX isogenic mutant showed these were comparable to those formed in the presence of saxagliptin, suggesting a probable role of this enzyme in biofilm formation by S. mutans UA159. The effects of both pepX deletion and DPP IV drugs on the proteome were studied using LC–MS/MS. Overall, this study highlights the potential of Sm-XPDAP as a novel anti-biofilm target and suggests a template molecule to synthesize lead compounds effective against this enzyme.

变形链球菌是引起牙本质病原体的龋齿，可产生X-脯氨酰二肽基肽酶（Sm-XPDAP，由pepX编码），一种丝氨酸蛋白酶，已知具有营养作用。考虑到蛋白酶作为病原体治疗靶标的潜力，本研究主要旨在研究Sm-XPDAP在促进与毒力有关的性状中的作用。二肽基肽酶（DPP IV）是在哺乳动物组织中发现的XPDAP类似酶，是II型糖尿病的众所周知的治疗靶标。基于通常用作抗人DPP IV药物的脂蛋白在抑制Sm-XPDAP后可能影响细菌生长的假设，我们确定了它们对变形链球菌的离体抗菌和抗生物膜活性。。通过结晶紫染色确定，测试的所有三种DPP IV药物均减少了生物膜的形成。为了将观察到的生物膜抑制作用与变形链球菌UA159中存在的人DPP IV类似物联系起来，产生了pepX等基因突变体。除了减少生物膜形成外，对由pepX等基因突变体形成的生物膜的CLSM研究表明，这些与在沙格列汀存在下形成的生物膜相当，表明该酶在变形链球菌UA159生物膜形成中的可能作用。pepX的效果使用LC-MS / MS研究了蛋白质组中的缺失和DPP IV药物。总的来说，这项研究突出了Sm-XPDAP作为新型抗生物膜靶标的潜力，并提出了一种模板分子来合成对这种酶有效的先导化合物。