Leukotoxic Activity of Aggregatibacter actinomycetemcomitans and Periodontal Attachment Loss
Leukotoxic Activity of Aggregatibacter actinomycetemcomitans and Periodontal Attachment Loss
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DOI：
10.1371/journal.pone.0104095
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发表时间：
2014-08-05
期刊：
影响因子：
3.7
通讯作者：
Claesson, Rolf
中科院分区：
文献类型：
--
作者：
Aberg, Carola Hoglund;Haubek, Dorte;Claesson, Rolf
伴放线菌聚集杆菌是一种革兰氏阴性牙周炎相关细菌，表达一种选择性影响白细胞的毒素。该白细胞毒素由属于该细菌物种的核心基因组的操纵子编码。白细胞毒素的表达的变化已被报道，并已分离出一个充分表征的特定克隆型（JP 2），这种细菌具有增强的白细胞毒素表达。特别是，JP2基因型的存在显着增加牙周附着丧失（AL）进展的风险。基于这些发现，我们假设白细胞毒性的变化与感染个体的疾病进展有关。本研究对239株临床分离的A.用不同的生物测定方法对伴放线菌进行了分析，并利用分子生物学技术对分离株的遗传特性进行了研究。对A.对伴放线菌进行纵向检查，并评估观察到的白细胞毒性变化与疾病进展的关系。我们的数据显示，高白细胞毒性与AL进展的风险增加相关。JP2基因型分离株均具有高白细胞毒性，而具有完整白细胞毒素启动子的分离株（非JP2基因型）在白细胞毒性方面表现出实质性变化。非JP2基因型分离株的遗传特征表明存在与JP2基因型相似的血清型B的高白细胞毒性基因型。根据这些结果，我们得出结论：A.伴随放线菌具有除前述JP2基因型之外的其它高毒性基因型。此外，本研究的结果进一步强调了白细胞毒素作为侵袭性牙周炎中关键毒力因子的重要性。
Aggregatibacter actinomycetemcomitans is a Gram-negative periodontitis-associated bacterium that expresses a toxin that selectively affects leukocytes. This leukotoxin is encoded by an operon belonging to the core genome of this bacterial species. Variations in the expression of the leukotoxin have been reported, and a well-characterized specific clonal type (JP2) of this bacterium with enhanced leukotoxin expression has been isolated. In particular, the presence of the JP2 genotype significantly increases the risk for the progression of periodontal attachment loss (AL). Based on these findings we hypothesized that variations in the leukotoxicity are linked to disease progression in infected individuals. In the present study, the leukotoxicity of 239 clinical isolates of A. actinomycetemcomitans was analysed with different bioassays, and the genetic peculiarities of the isolates were related to their leukotoxicity based on examination with molecular techniques. The periodontal status of the individuals sampled for the presence of A. actinomycetemcomitans was examined longitudinally, and the importance of the observed variations in leukotoxicity was evaluated in relation to disease progression. Our data show that high leukotoxicity correlates with an enhanced risk for the progression of AL. The JP2 genotype isolates were all highly leukotoxic, while the isolates with an intact leukotoxin promoter (non-JP2 genotypes) showed substantial variation in leukotoxicity. Genetic characterization of the non-JP2 genotype isolates indicated the presence of highly leukotoxic genotypes of serotype b with similarities to the JP2 genotype. Based on these results, we conclude that A. actinomycetemcomitans harbours other highly virulent genotypes besides the previously described JP2 genotype. In addition, the results from the present study further highlight the importance of the leukotoxin as a key virulence factor in aggressive forms of periodontitis.