Porphyromonas gingivalis is a keystone bacterium in the oral microbial communities that elicits a dysbiosis between the microbiota and the host. Therefore, inhibition of this organism in dental plaques has been one of the strategies for preventing and treating chronic periodontitis. We previously identified a Streptococcal ArcA derived Anti‐P gingivalils Peptide (SAPP) that in vitro, is capable of repressing the expression of several virulence genes in the organism. This leads to a significant reduction in P gingivalis virulence potential, including its ability to colonize on the surface of Streptococcus gordonii, to invade human oral epithelial cells, and to produce gingipains. In this study, we showed that SAPP had minimal cytotoxicity to human oral keratinocytes and gingival fibroblasts. We observed that SAPP directly bound to the cell surface of P gingivalis, and that alterations in the sequence at the N‐terminus of SAPP diminished its abilities to interact with P gingivalis cells and repressed the expression of virulence genes. Most strikingly, we demonstrated using an ex‐vivo assay that besides its inhibitory activity against P gingivalis colonization, SAPP could also reduce the levels of several other oral Gram‐negative bacteria strongly associated with periodontitis in multispecies biofilms. Our results provide a platform for the development of SAPP‐targeted therapeutics against chronic periodontitis.

中文翻译：

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SAPP 作为针对牙龈卟啉单胞菌的特异性肽抑制剂的表征和开发。


牙龈卟啉单胞菌是口腔微生物群落中的关键细菌，可引起微生物群与宿主之间的菌群失调。因此，抑制牙菌斑中的这种微生物已成为预防和治疗慢性牙周炎的策略之一。我们之前鉴定了一种链球菌 ArcA 衍生的抗牙龈卟啉单胞菌肽 (SAPP)，它在体外能够抑制生物体中几种毒力基因的表达。这导致牙龈卟啉单胞菌毒力潜力显着降低，包括其在戈登链球菌表面定殖、侵入人类口腔上皮细胞和产生牙龈蛋白酶的能力。在这项研究中，我们表明 SAPP 对人口腔角质形成细胞和牙龈成纤维细胞具有最小的细胞毒性。我们观察到SAPP直接与牙龈卟啉单胞菌细胞表面结合，并且SAPP N末端序列的改变降低了其与牙龈卟啉单胞菌细胞相互作用的能力并抑制毒力基因的表达。最引人注目的是，我们使用离体测定证明，除了对牙龈卟啉单胞菌定植具有抑制活性外，SAPP还可以降低多物种生物膜中与牙周炎密切相关的其他几种口腔革兰氏阴性细菌的水平。我们的结果为开发针对慢性牙周炎的 SAPP 靶向疗法提供了平台。