Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype
Virulence of Porphyromonas gingivalis is altered by substitution of fimbria gene with different genotype
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DOI：
10.1111/j.1462-5822.2006.00825.x
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Amano, Atsuo
中科院分区：
文献类型：
--
作者：
Kato, Takahiro;Kawai, Shinji;Amano, Atsuo
牙龈卟啉单胞菌（Porphyromonas gingivalis）是一种牙周病病原菌，根据其菌毛亚基fimA基因的多样性，将其菌毛分为6种基因型。表明具有II型菌毛的牙龈卟啉单胞菌菌株比I型菌株毒力更强。在本研究中，我们产生的突变体，其中fimA被替换为不同的基因型，研究II型菌毛的毒力。使用质粒载体，将ATCC 33277（I型菌株）的fimA替换为II型fimA，将OMZ 314（II型菌株）的fimA替换为I型fimA。用II型fimA取代I型fimA增强了细菌对上皮细胞的粘附/侵袭，而用I型fimA取代导致效率降低。细菌入侵后，II型克隆迅速降解细胞桩蛋白和粘着斑激酶，并抑制细胞迁移，而I型克隆和Delta fimA突变体没有。BIAcore分析表明，II型菌毛对其受体α 5 β 1整合素的粘附能力比I型菌毛更强。在小鼠脓肿模型中，II型克隆显著诱导血清IL-1 β和IL-6以及其他感染症状。这些结果表明，II型菌毛是牙龈卟啉单胞菌毒力的关键决定因素。
Porphyromonas gingivalis is a periodontal pathogen whose fimbriae are classified into six genotypes based on the diversity of the fimA genes encoding each fimbria subunit. It was suggested that P. gingivalis strains with type II fimbriae were more virulent than type I strains. For the present study, we generated the mutants in which fimA was substituted with different genotypes to study virulence of type II fimbriae. Using plasmid vectors, fimA of ATCC33277 (type I strain) was substituted with type II fimA, and that of OMZ314 (type II strain) with type I fimA. The substitution of type I fimA with type II enhanced bacterial adhesion/invasion to epithelial cells, whereas substitution with type I fimA resulted in diminished efficiency. Following bacterial invasion, type II clones swiftly degraded cellular paxillin and focal adhesion kinase, and inhibited cellular migration, whereas type I clones and Delta fimA mutants did not. BIAcore analysis demonstrated that type II fimbriae possess greater adhesive abilities for their receptor alpha 5 beta 1-integrin than those of type I. In a mouse abscess model, the type II clones significantly induced serum IL-1 beta and IL-6, as well as other infectious symptoms. These results suggest that type II fimbriae are a critical determinant of P. gingivalis virulence.