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首页> 外文期刊>Infection and immunity >Translocation of Porphyromonas gingivalis Gingipain Adhesin Peptide A44 to Host Mitochondria Prevents Apoptosis
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Translocation of Porphyromonas gingivalis Gingipain Adhesin Peptide A44 to Host Mitochondria Prevents Apoptosis

机译：牙龈卟啉单胞菌银杏粘附素肽A44转位至宿主线粒体可防止细胞凋亡

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Porphyromonas gingivalis, a Gram-negative oral anaerobe, is associated with periodontal diseases that, in some form, affect up to 80% of the U.S. population. The organism is highly proteolytic, and noncatalytic adhesin domains of the major proteases, gingipains, are involved in bacterium-host interactions. Recently, we showed that gingipain adhesin peptide A44 hijacks the host's clathrin-dependent endocytosis system, allowing the peptide and whole bacteria to be internalized by epithelial cells. In the present study, we found by cell fractionation assays and confocal microscopy that peptide A44 translocated to host mitochondria. Cell viability assays and quantitative real-time PCR showed that the peptide interacted with the cell death machinery by triggering upregulation of antiapoptotic factors bcl-2 and bcl-XL and prevented staurosporine-induced apoptosis for up to 12 h. We confirmed these findings with Western blot analyses of caspase-9 activation in time course experiments with staurosporine. Finally, we verified a similar antiapoptotic effect for P. gingivalis, showing for the first time that the organism manipulated mitochondrial functions during the first hours of infection, thus resisting host cell clearance by apoptosis of infected cells. This mechanism may enable the bacteria to persist in the protected cellular environment until the next step in pathogenesis, progression or resolution of infection.
机译：革兰氏阴性口腔厌氧菌 Porphyromonas gingivalis 与牙周疾病有关，这种疾病以某种形式影响了多达80％的美国人口。该生物是高度蛋白水解的，主要蛋白酶牙龈蛋白酶的非催化粘附素结构域参与细菌-宿主相互作用。最近，我们发现姜黄素粘附素肽A44劫持了宿主的网格蛋白依赖性内吞系统，使该肽和整个细菌被上皮细胞内化。在本研究中，我们通过细胞分级分析和共聚焦显微镜发现，肽A44易位至宿主线粒体。细胞活力测定和实时定量PCR结果表明，该肽通过触发抗凋亡因子 bcl-2 和 bcl-XL 的上调而与细胞死亡机制相互作用，并阻止了星形孢菌素-诱导细胞凋亡长达12小时。我们用星形孢菌素在时程实验中用caspase-9激活的蛋白质印迹分析证实了这些发现。最后，我们证实了对 P具有相似的抗凋亡作用。齿龈炎，首次表明该生物体在感染的最初几个小时内操纵了线粒体功能，从而抵抗了被感染细胞凋亡引起的宿主细胞清除。这种机制可以使细菌在受保护的细胞环境中持续存在，直到感染的发病机理，进展或解决的下一步。

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