Bao K, Oscarsson J, Gehring P, Grossmann J, Belibasakis G N, Bostanci N
Division of Oral Health and Periodontology, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
Oral Microbiology, Department of Odontology, Umeå University, Umeå, Sweden.
J Dent Res. 2025 Jun 26:220345251337745. doi: 10.1177/00220345251337745.
is the only known oral bacterium with a functional type VI secretion system (T6SS) that acts against . Bacteria use the T6SS to deliver toxic effectors into bacterial or eukaryotic cells during interbacterial competition or host colonization. To date, the T6SS of has not been demonstrated to participate in antieukaryotic activity, nor have the cytotoxic effectors involved been identified. Here, we identified 2 T6SS effectors in , a glycosyl hydrolase (Glh) and a phospholipase D (Tle5), which, upon inactivation of their respective genes, together resulted in abolished T6SS activity against in multispecies biofilms. Next, we probed the role of the 2 T6SS effectors in host-cell interactions using gingival keratinocytes. Interestingly, although neither of the effectors appeared to contribute to the acute inflammatory response directly, the co-presence of both species reduced the inflammatory effect, likely due to the T6SS-dependent elimination of , hence decreasing the bacterial abundance. This reduction was not observed using mutants lacking the effectors or the T6SS "tube" core protein, hemolysin co-regulated protein (Hcp). Here, we show that the T6SS effectors in have distinct functions in eukaryotic versus bacterial cell interactions. Hence, these T6SS effectors may represent novel mechanisms of interaction between bacteria and the oral-mucosal barrier, offering potential therapeutic targets for managing periodontal pathogens.
是唯一已知的具有功能性VI型分泌系统（T6SS）且能作用于……的口腔细菌。细菌在种间竞争或宿主定殖过程中利用T6SS将毒性效应蛋白传递到细菌或真核细胞中。迄今为止，……的T6SS尚未被证明参与抗真核生物活性，所涉及的细胞毒性效应蛋白也未被鉴定出来。在此，我们在……中鉴定出2种T6SS效应蛋白，一种糖基水解酶（Glh）和一种磷脂酶D（Tle5），在它们各自的基因失活后，共同导致多物种生物膜中针对……的T6SS活性丧失。接下来，我们使用牙龈角质形成细胞探究了这2种T6SS效应蛋白在宿主细胞相互作用中的作用。有趣的是，尽管这两种效应蛋白似乎都没有直接促成急性炎症反应，但两种细菌同时存在时炎症效应降低，这可能是由于T6SS依赖的……清除，从而降低了细菌丰度。使用缺乏效应蛋白或T6SS“管”核心蛋白溶血素共调节蛋白（Hcp）的……突变体时未观察到这种降低。在此，我们表明……中的T6SS效应蛋白在真核细胞与细菌细胞相互作用中具有不同功能。因此，这些T6SS效应蛋白可能代表了细菌与口腔黏膜屏障之间相互作用的新机制，为管理牙周病原体提供了潜在的治疗靶点。
