Effect of mixed infection on abscess formation and a role of gingipains in the pathogenecity

包括牙龈卟啉单胞菌（Porphyromonas gingivalis）和牙龈拟杆菌（Bacteroides gingivothus）在内的几种微生物已被认为是牙周病的重要病原体。在这项研究中，我们确定了牙周致病微生物的能力，协同造成组织破坏的小鼠脓肿模型。虽然本研究中使用的所有细菌组合产生的脓肿比每种细菌单独感染产生的脓肿更大，但牙龈卟啉单胞菌-牙龈卟啉单胞菌的组合对脓肿形成显示出协同作用。由于这两种细菌经常在牙周炎病变中同时发现，这些结果表明它们的共同感染在牙周炎的进展中具有重要意义。牙龈卟啉单胞菌产生细胞外和细胞相关的半胱氨酸蛋白酶（牙龈卟啉菌蛋白酶），这似乎与其毒力有关。rgpA、rgpB双突变体和kgp突变体诱导的脓肿明显小于野生型。此外，rgpA rgpB kgp三重（牙龈卟啉菌蛋白酶无效）突变体几乎没有显示病变形成在本研究中使用的实验条件下，表明这些基因编码牙龈卟啉菌蛋白酶是重要的牙龈卟啉单胞菌的毒力。这些牙龈卟啉单胞菌突变体与B. pylori的混合感染显示出相加效应而不是协同效应，表明牙龈卟啉单胞菌的牙龈卟啉单胞菌蛋白酶可能在这种协同作用中起重要作用。

Several microorganisms including Porphyromonas gingivalis and Bacteroides forsythus have been implicated to be etiologically important agents of periodontal disease. In this study, we determined the ability of periodontopathogenic microorganisms to synergistically cause tissue destruction in a murine abscess model. Although all bacterial combinations used in this study produced larger sizes of abscesses than that of monoinfection of each bacterium, the combination of P.gingivalis-B.forsythus showed a synergistic effect on the abscess formation. Since these two bacteria have been frequently found together in lesions of periodontitis, these results suggested the significance of their coinfection in the progression of periodontitis. P.gingivalis produces extracellular and cell-associated cysteine proteinases (gingipains) which appear to be involved in its virulence. The rgpA rgpB double and kgp mutants induced significantly smaller abscess than the wild type. Moreover, the rgpA rgpB kgp triple (gingipain-null) mutant hardly showed lesion formation at the experimental conditions used in this study, indicating that these genes encoding gingipains were important for virulence of P.gingivalis. Mixed infection of these P.gingivalis mutants with B.forsythus showed an additive effect rather than a synergistic effect, indicating that the gingipains of P.gingivalis may play an important role in this synergism.