Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection.
Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection.
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DOI：
10.1016/j.chom.2015.06.004
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发表时间：
2015-07-08
影响因子：
30.3
通讯作者：
Engel J
中科院分区：
文献类型：
--
作者：
Mirrashidi KM;Elwell CA;Verschueren E;Johnson JR;Frando A;Von Dollen J;Rosenberg O;Gulbahce N;Jang G;Johnson T;Jäger S;Gopalakrishnan AM;Sherry J;Dunn JD;Olive A;Penn B;Shales M;Cox JS;Starnbach MN;Derre I;Valdivia R;Krogan NJ;Engel J
沙眼衣原体是生殖器和眼睛感染的主要原因，目前还没有针对这些感染的疫苗。进入宿主细胞后，沙眼衣原体驻留在一个膜结合的隔间--包涵体--并分泌被认为调节宿主-细菌界面的包涵膜蛋白(Incs)。为了扩大我们对InC功能的理解(S)，我们对推测的沙眼衣原体Incs进行了亲和纯化-质谱分析(AP-MS)。我们确定了38/58个Inc的Inc与人类的相互作用，宿主过程中的浓缩与衣原体的细胞内生命周期一致。INC靶标和病毒蛋白之间有显著重叠，表明专性细胞内微生物之间存在共同的致病机制。INCE与逆转录聚合体的分选连接素(SNXs)5/6结合，导致SNX5/6重新定位到包涵体膜上，并增强了包涵体膜管的形成。逆转录病毒组分的耗尽增强了后代的产量，揭示了逆转录病毒对衣原体感染的限制。这项研究证明了蛋白质组学在揭示遗传挑战微生物中宿主与病原体相互作用方面的价值。
Chlamydia trachomatis is a leading cause of genital and ocular infections for which no vaccine exists. Upon entry into host cells, C. trachomatis resides within a membrane bound compartment—the inclusion--and secretes inclusion membrane proteins (Incs) that are thought to modulate the host-bacterium interface. To expand our understanding of Inc function(s), we subjected putative C. trachomatis Incs to affinity purification-mass spectroscopy (AP-MS). We identified Inc-human interactions for 38/58 Incs with enrichment in host processes consistent with Chlamydia’s intracellular lifecycle. There is significant overlap between Inc targets and viral proteins, suggesting common pathogenic mechanisms among obligate intracellular microbes. IncE binds to sorting nexins (SNXs) 5/6, components of the retromer, resulting in SNX5/6 relocalization to the inclusion membrane and enhanced inclusion membrane tubulation. Depletion of retromer components enhances progeny production, revealing that retromer restricts Chlamydia infection. This study demonstrates the value of proteomics in unveiling host-pathogen interactions in genetically challenging microbes.