The inclusion membrane protein IncS is critical for initiation of the Chlamydia intracellular developmental cycle.
The inclusion membrane protein IncS is critical for initiation of the Chlamydia intracellular developmental cycle.
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DOI：
10.1371/journal.ppat.1010818
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发表时间：
2022-09
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
所有衣原体属都是专性细胞内细菌，严格在膜结合区室（内含物）的内腔中经历独特的双相发育周期。衣原体特异性III型分泌的效应物，称为包涵体膜蛋白（Inc），嵌入包涵体膜中。通过发育周期的进展，特别是从感染性（EB）细菌转化为复制性（RB）细菌的早期事件，对细胞内复制很重要，但了解甚少。在这里，我们确定了包涵体膜蛋白IncS作为衣原体发展的关键因素。我们表明，一个C。沙眼衣原体条件突变体在人细胞中从EB向RB的转化中受损，并且C.在衣原体感染的小鼠模型中，鼠伤寒沙门氏菌突变体细菌不能发育。因此，IncS代表了用于细菌性传播感染的主要原因的治疗干预的有希望的靶标。对于专性细胞内细菌病原体的细胞内生活方式来说是必需的或非常重要的细菌因子的鉴定和表征，对于专性细胞内细菌病原体，存在有限的遗传工具，提出了独特的挑战。在这里，我们提供了一个蓝图，以产生条件突变体沙眼衣原体和衣原体muridarum，通过结合现有的遗传工具，包括诱导型启动子，是响应衣原体感染的小鼠模型。作为一个概念的证明，我们提出了一个条件突变体的衣原体包涵体膜蛋白，并表明它是受损的早期阶段的发展周期。我们的研究构成了衣原体研究的一个重大方法学进步，并进一步加深了我们对细菌因素在发育周期中的作用的理解。
All Chlamydia species are obligate intracellular bacteria that undergo a unique biphasic developmental cycle strictly in the lumen of a membrane bound compartment, the inclusion. Chlamydia specific Type III secreted effectors, known as inclusion membrane proteins (Inc), are embedded into the inclusion membrane. Progression through the developmental cycle, in particular early events of conversion from infectious (EB) to replicative (RB) bacteria, is important for intracellular replication, but poorly understood. Here, we identified the inclusion membrane protein IncS as a critical factor for Chlamydia development. We show that a C. trachomatis conditional mutant is impaired in transition from EB to RB in human cells, and C. muridarum mutant bacteria fail to develop in a mouse model of Chlamydia infection. Thus, IncS represents a promising target for therapeutic intervention of the leading cause of sexually transmitted infections of bacterial origin. The identification and characterization of bacterial factors that are essential, or highly important, to the intracellular life style of obligate intracellular bacterial pathogens, for which limited genetic tools exist, present unique challenges. Here, we offer a blueprint to generate conditional mutants in Chlamydia trachomatis and Chlamydia muridarum, by combining existing genetic tools for Chlamydia, including an inducible promoter that is responsive in a murine model of Chlamydia infection. As a proof of concept, we present a conditional mutant in a Chlamydia inclusion membrane protein and show that it is impaired in the early stages of the developmental cycle. Our study constitutes a major methodological advance to the study of Chlamydia and furthers our understanding of the bacterial factors contributing to progression through the developmental cycle.
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影响因子：
3.7
作者：
Grieshaber NA;Chiarelli TJ;Appa CR;Neiswanger G;Peretti K;Grieshaber SS
通讯作者：
Grieshaber SS
DOI：
10.3791/60848
发表时间：
2020-01-30
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Keb G;Fields KA
通讯作者：
Fields KA
影响因子：
30.3
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
通讯作者：
Engel J
影响因子：
6.7
作者：
Derré I;Pypaert M;Dautry-Varsat A;Agaisse H
通讯作者：
Agaisse H
影响因子：
6.2
作者：
de la Maza LM;Darville TL;Pal S
通讯作者：
Pal S