The highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans: evolutionary aspects, epidemiology and etiological role in aggressive periodontitis
The highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans: evolutionary aspects, epidemiology and etiological role in aggressive periodontitis
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DOI：
10.1111/j.1600-0463.2010.02665.x
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发表时间：
2010-09-01
期刊：
影响因子：
2.8
通讯作者：
Haubek, Dorte
中科院分区：
文献类型：
--
作者：
Haubek, Dorte
多年来，人们一直关注口腔细菌伴放线菌聚集杆菌，作为一种可能涉及青少年侵袭性牙周炎的病原学。A.伴放线菌是一种白细胞毒素，能够杀死免疫系统的重要细胞。群体遗传分析表明，该群体的结构是一致的。伴放线菌主要是克隆的，其进化谱系与血清型相对应。已发现血清型B的一种特殊的高白细胞毒性克隆（JP 2）。JP2克隆，估计起源约2400年前，被认为是高度保守的，基于对收集的JP2克隆菌株的分析，这些菌株来自20多年来不同来源的个体，生活在地理上广泛分布。尽管在A.在放线菌伴放线菌中，JP2克隆菌株构成了独特的克隆类型，其特征包括白细胞毒素操纵子中的530个碱基对缺失，该缺失与克隆的增强的白细胞毒性活性有关。对A. JP2克隆的地理分布进行了定位。放线菌共生体的研究表明，其定殖主要限于非洲裔个体。特征性突变，这使得JP2克隆分离物从地中海地区，以区分从西非，包括佛得角群岛的分离物，表明JP2克隆最初出现在非洲的地中海地区的一个独特的基因型，随后传播到西非，从那里它可能已经转移到美洲大陆在跨大西洋奴隶贸易。尽管与非洲大陆地理分离了几个世纪，但非洲血统的个体持续选择性殖民的发现表明JP2克隆可能具有独特的寄主向性。需要进一步研究来阐明地中海和西非人口明显选择性殖民的原因。将A.放线菌共生菌似乎在侵袭性牙周炎的病因学中起着突出的作用相比，其他克隆类型的物种。而A.一般来说，伴随放线菌被认为是常驻口腔微生物群的机会致病菌，JP2克隆具有与外源致病菌相似的特征。JP2以外的克隆类型可以从健康和牙周病个体中分离，而JP2克隆主要从牙周病个体中分离。正如在摩洛哥的一项前瞻性队列研究中所证明的那样，其中JP2克隆是地方性存在的，牙菌斑中该克隆的存在使侵袭性牙周炎的发展风险显著增加，这表明JP2克隆是青少年侵袭性牙周炎的重要病原体。支持A的JP2以外的克隆类型的关联。放线菌共生菌与侵袭性牙周炎的关系也已被证实，但这种关系要弱得多。近一半的JP2克隆携带者在两年的随访期间被发现持续感染，这表明JP2克隆的定殖稳定性水平与先前报道的非JP2克隆类型的A。伴放线菌侵袭性牙周炎的相对风险是最高的个人与稳定的JP2克隆定植。虽然所用的方法是不定量的，这一发现增加了证据的因果关系的JP2克隆在侵袭性牙周炎…
For many years, attention has been given to the oral bacterium Aggregatibacter actinomycetemcomitans, as a species possibly implicated in the etiology of aggressive periodontitis in adolescents. One of the major virulence factors of A. actinomycetemcomitans is the leukotoxin which is able to kill important cells of the immune system. As demonstrated in population genetic analyses, the population structure of A. actinomycetemcomitans is mainly clonal with evolutionary lineages corresponding to the serotypes. A particular highly leukotoxic clone (JP2) of serotype b has been discovered. The JP2 clone, with an estimated origin some 2400 years ago, is found to be highly conserved, based on analyses of a collection of JP2 clone strains collected through more than 20 years from individuals of diverse origin and living geographically widespread. Despite demonstration of minor evolutionary changes within the genome of JP2 clone strains of A. actinomycetemcomitans, the JP2 clone strains constitute a unique clonal type, the characteristics of which include a 530 basepair deletion in the leukotoxin operon implicated in the enhanced leukotoxic activity of the clone. Mapping of the geographic occurrence of the JP2 clone of A. actinomycetemcomitans has revealed that its colonization is largely restricted to individuals of African descent. Characteristic mutations, which allow JP2 clone isolates from the Mediterranean region to be distinguished from isolates from West Africa, including the Cape Verde islands, suggest that the JP2 clone initially emerged as a distinct genotype in the Mediterranean region of Africa and subsequently spread to West Africa, from where it might have been transferred to the American continent during the transatlantic slave trade. The finding of a sustained selective colonization of individuals of African descent, despite geographical separation from the African continent for centuries, suggests that the JP2 clone might have a distinct host tropism. Further studies are needed to elucidate the reasons for the apparent selective colonization of the Mediterranean and Western African populations. The JP2 clone of A. actinomycetemcomitans appears to play a prominent role in the etiology of aggressive periodontitis compared to other clonal types of the species. While A. actinomycetemcomitans, in general, is considered an opportunistic pathogen of the resident oral microbiota, the JP2 clone has features similar to those of an exogenous pathogen. Clonal types other than JP2 can be isolated from healthy as well as periodontally diseased individuals, whereas the JP2 clone has been isolated primarily from periodontally diseased individuals. As demonstrated in a prospective cohort study in Morocco, where the JP2 clone is endemically present, the presence of this clone in dental plaque confers a remarkably increased risk for development of aggressive periodontitis, suggesting that the JP2 clone is an important etiological agent of aggressive periodontitis in adolescents. Support for association of clonal types other than JP2 of A. actinomycetemcomitans with aggressive periodontitis has also been provided, but the association is much weaker. Nearly half of the JP2 clone carriers were found to be persistently infected during a two-year follow-up period, which indicates a level of stability of colonization with the JP2 clone similar to that previously reported for non-JP2 clonal types of A. actinomycetemcomitans. The relative risk of aggressive periodontitis is highest for individuals with stable JP2 clone colonization. Although the method used is not quantitative, this finding adds to the evidence for a causal role of the JP2 clone in aggressive periodontitis …