Chlamydia trachomatis Subverts Alpha-Actinins To Stabilize Its Inclusion.
Chlamydia trachomatis Subverts Alpha-Actinins To Stabilize Its Inclusion.
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DOI：
10.1128/spectrum.02614-22
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发表时间：
2023-02-14
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
沙眼衣原体是性传播细菌疾病的主要原因，也是全球健康负担。作为一种专性细胞内病原体，衣原体进化出许多策略来操纵其宿主并建立其细胞内生态位，称为包涵体。沙眼衣原体重组宿主肌动蛋白细胞骨架，在包涵体周围形成支架，加强生长的包涵体膜。为了控制肌动蛋白支架的动力学和形成，衣原体表达效应物InaC/CT813，激活宿主GTPase RhoA。在这里，我们发现InaC通过宿主肌动蛋白交联蛋白α-肌动蛋白1和4来稳定肌动蛋白支架。我们证明α-肌动蛋白以inac依赖的方式被招募到包涵体膜上，并与包涵体的肌动蛋白支架结合。小干扰RNA （siRNA）介导的α-肌动蛋白敲低会对肌动蛋白支架的频率产生差异，并损害其包合稳定性，使其容易破裂和被非离子洗涤剂提取。总的来说，我们的数据确定了新的宿主效应物，这些效应物被InaC破坏以稳定肌动蛋白支架，突出了InaC作为衣原体感染期间宿主细胞骨架网络的关键调节剂的多功能性。重要性：尽管使用抗生素，复发性沙眼衣原体感染对男性和女性的生殖道造成重大损害。在没有预防性疫苗的情况下，了解衣原体致病的毒力机制至关重要。在这种情况下，操纵宿主细胞骨架是衣原体发育的关键组成部分。肌动蛋白支架增强了衣原体感染液泡的完整性，这是衣原体与宿主环境之间的关键屏障。在之前的研究中，我们已经证实InaC会选择RhoA来促进包涵体周围肌动蛋白支架的形成，现在我们发现衣原体劫持了一类新的宿主效应物α-肌动蛋白，来交联这些支架并进一步稳定包涵体。我们还确定了衣原体效应InaC的核心功能是在衣原体感染期间调节细胞骨架稳定性。最终，这项工作扩展了我们对细菌病原体如何通过靶向基本宿主效应蛋白来破坏肌动蛋白细胞骨架的理解。
Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease and a global health burden. As an obligate intracellular pathogen, Chlamydia has evolved many strategies to manipulate its host and establish its intracellular niche called the inclusion. C. trachomatis reorganizes the host actin cytoskeleton to form scaffolds around the inclusion and reinforce the growing inclusion membrane. To control the kinetics and formation of actin scaffolds, Chlamydia expresses the effector InaC/CT813, which activates the host GTPase RhoA. Here, we have discovered that InaC stabilizes actin scaffolds through the host actin cross-linking proteins α-actinins 1 and 4. We demonstrate that α-actinins are recruited to the inclusion membrane in an InaC-dependent manner and associate with actin scaffolds that envelop the inclusion. Small interfering RNA (siRNA)-mediated knockdown of α-actinins differentially regulate the frequency of actin scaffolds and impair inclusion stability, leaving them susceptible to rupture and to nonionic detergent extraction. Overall, our data identify new host effectors that are subverted by InaC to stabilize actin scaffolds, highlighting the versatility of InaC as a key regulator of the host cytoskeletal network during Chlamydia infection. IMPORTANCE Despite antibiotics, recurrent C. trachomatis infections cause significant damage to the genital tract in men and women. Without a preventative vaccine, it is paramount to understand the virulence mechanisms that Chlamydia employs to cause disease. In this context, manipulation of the host cytoskeleton is a critical component of Chlamydia development. Actin scaffolds reinforce the integrity of Chlamydia’s infectious vacuole, which is a critical barrier between Chlamydia and the host environment. Having previously established that InaC co-opts RhoA to promote the formation of actin scaffolds around the inclusion, we now show that Chlamydia hijacks a new class of host effectors, α-actinins, to cross-link these scaffolds and further stabilize the inclusion. We also establish that a core function of the chlamydial effector InaC is the regulation of cytoskeletal stability during Chlamydia infection. Ultimately, this work expands our understanding of how bacterial pathogens subvert the actin cytoskeleton by targeting fundamental host effector proteins.
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影响因子：
6.4
作者：
Haines A;Wesolowski J;Ryan NM;Monteiro-Brás T;Paumet F
通讯作者：
Paumet F
影响因子：
--
作者：
Otey, CA;Carpen, O
通讯作者：
Carpen, O
DOI：
10.1073/pnas.79.14.4280
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
MEYER, RK;SCHINDLER, H;BURGER, MM
通讯作者：
BURGER, MM
影响因子：
13.3
作者：
Al-Younes, Hesham M.;Al-Zeer, Munir A.;Meyer, Thomas F.
通讯作者：
Meyer, Thomas F.
影响因子：
30.3
作者：
Kumar Y;Valdivia RH
通讯作者：
Valdivia RH