Development of clinical diagnostic test and DNA vaccination based on genotypes of the periodontal pathogen

成人牙周炎是一种高度破坏性的慢性炎症性疾病，是由牙周细菌的一小部分复杂作用引起的。其中，牙周炎是一种真正的牙周病原体。这种微生物在牙周炎患者中经常被检测到，而据报道，它在牙周健康的人中发生的频率很高，没有明显的牙龈炎症。牙周健康的人和牙周炎患者体内的微生物在毒力上可能存在差异。然而，目前尚不清楚牙周炎是否只有在牙龈假单胞菌毒力株(S)存在的情况下才会发生，或者是否其他宿主因素，如遗传背景和环境压力，可能在该组织感染的个体中对疾病的发生有决定性的影响。牙龈卟啉单胞菌的fimA基因编码fimbrin(菌毛的一种亚单位蛋白)，为…在这些菌株中，又分为6种基因类型(I-V和Ib型)，这些基因类型先前被证明与自然人群中的成人牙周炎有关。在这里，使用OUSE脓肿模型和培养的上皮细胞检测了不同FIMA菌株之间的毒力异质性。给雌性BALB/c小鼠皮下注射代表6种fimA的13株牙龈假单胞菌菌悬液，测定血清唾液酸浓度作为炎症指标。同时还检测了牙龈假单胞菌对上皮细胞的感染情况。II型FIMA病毒最显著地增加了血清唾液酸浓度，并在TB、IV和V型菌株允许的小鼠模型中清楚地显示出其他感染症状。然而，I型和III型菌株引起的宿主反应较弱，II型菌株侵袭上皮细胞的程度明显高于其他菌株。伴随着上皮细胞的侵袭，Paxlin和FAK蛋白的降解和磷酸化丢失明显。I型和III型菌株对蛋白质的侵袭和降解能力均低于II型菌株。II型菌株的FIMA突变体显然在小鼠模型和培养的上皮细胞中都失去了感染能力。这些发现表明，FIMA基因变异是牙周炎患者牙周炎程度的决定因素。

Adult periodontitis is a highly destructive chronic inflammatory disease resulting from the complex actions of a small subset of periodontal bacteria Among them, Porphyromonas girigivalis has been characterized as a bona fide periodontal pathogen.This microorganism has been frequently detected in patients with periodontitis, while it reportedly occurs at a tower frequency in periodontally healthy individuals without marked gingival inflammation. There may be diversities in virulence among the organisms harbored by individuals who are periodontally healthy and those with periodontitis. However, it is still unknown whether periodontitis can develop only in the presence of virulent strain(s) of P. gingivalis, or if other host factors, such as genetic background and environmental stress, may have a determining influence in the initiation of the disease in individuals infected by the organism.The fimA gene of Porphyromonas gingivalis, encoding fimbrillin (a subunit protein of fimbriae) was … More classified into six genotypes (types I-V & Ib) among the strains, and the genotypes were previously shown to be related with adult periodontitis in the natural population. Here, virulence heterogeneity among the different fimA strains was examined using a *ouse abscess model and cultured epithelial cells. Bacterial suspensions of thirteen P. gingivalis strains representing sixfimA types were subcutaneously injected to female BALB/c mice, and serum sialic acid concentration was assayed as a quantitative of inflammatory parameter. Infection of P. gingivalis strains to epithelial cells was also examined. Type II fimA oraganisms most significantly increased serum sialic acid concentration, and clearly showed other infectious symptoms in a mouse model,allowed by types Tb, IV and V strains. Whereas, types I and III strains caused weak host responses.The type II strain invaded epithelial cells significantly greater than the other strains. Accompanied with the invasion of epithelial cells, degradations of paxillin and FAK proteins and loss of their phosphorylation were markedly observed. The invasion and degradation of the proteins by type I and III strains were less than those of the type II strain. The fimA mutants of type II strains clearly lost their infectious abilities both in a mouse model and culture epithelial cells. These findings suggest that fimA genotypic variation is a determinant of virulence of P. gingivalis.Periodontitis Less