Porphyromonas gingivalis, a keystone pathogen in periodontitis, secretes an array of virulence factors including gingipains via the type IX secretion system (T9SS). Inactivation of any component of the T9SS leads to the accumulation of secreted proteins in unprocessed and, in the case of progingipains, inactive forms in the periplasm. To cast light on the paradox that active gingipains are essential for P. gingivalis fitness in vivo but a functional T9SS is not (Frontiers in Cellular and Infection Microbiology, 2017, 7:378), we have compared virulence of wild‐type P. gingivalis W83 and the gingipain‐null strain with isogenic mutants deficient in individual T9SS components. Using an in vivo subcutaneous chamber mouse model of infection, gingipain‐null strain secretion mutants showed no virulence, but their pathogenic potential was reconstituted by coinfection with a low number of the parental strain. Apparently the same mechanism compensated fitness of mutants lacking functional T9SS the transposon library. In contrast to the parental strain, all mutants elicited significantly lower but an effective inflammatory immune response, which cleared infection and prevented systemic dissemination of P. gingivalis to organs. There were no significant differences in immune responses to different secretion mutants, which were generally more stimulatory than the gingipain‐null strain. Together, these results indicate that functional T9SS is essential for P. gingivalis virulence apparently through delivery of active gingipains to the bacterial surface. Therefore, T9SS is a legitimate target for drug development to treat periodontitis.

中文翻译：

---

IX型分泌系统对于表达与齿龈卟啉单胞菌相关的齿龈蛋白酶相关的毒力至关重要。

牙龈卟啉单胞菌（Porphyromonas gingivalis）是牙周炎的关键病原体，它通过IX型分泌系统（T9SS）分泌一系列毒力因子，包括牙龈蛋白酶。T9SS的任何成分失活都会导致分泌的蛋白质在未经加工的情况下积聚，而在使用progingipains的情况下，其在周质中处于失活状态。对悖论活性牙龈菌蛋白酶是必不可少的投光牙龈卟啉菌体内健身但功能T9SS不是（在蜂窝与感染微生物前沿，2017年，7：378），我们比较野生型毒力牙龈W83和带有等位基因突变体的gingipain-null菌株缺乏单个T9SS组分。使用体内皮下腔内感染小鼠模型，牙龈蛋白酶无效的菌株分泌突变体没有显示出毒力，但是通过与少量亲本菌株的共感染可以重建它们的致病潜力。显然，相同的机制补偿了缺乏功能性T9SS转座子文库的突变体的适应性。与亲本菌株相比，所有突变体均引起明显降低但有效的炎症免疫反应，从而清除了感染并阻止了牙龈卟啉单胞菌的系统性传播。到器官。对不同分泌突变体的免疫反应没有显着差异，这些突变体通常比牙龈肽无效菌株更具刺激性。总之，这些结果表明，功能性T9SS对于牙龈卟啉单胞菌毒力显然是必需的，这是通过向细菌表面递送活性牙龈蛋白酶来实现的。因此，T9SS是治疗牙周炎的药物开发的合法目标。