Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute its biological activities.
Mycoplasma pneumoniae CARDS toxin exploits host cell endosomal acidic pH and vacuolar ATPase proton pump to execute its biological activities.
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支原体肺炎卡毒素毒素利用宿主细胞内体酸性pH和液泡ATPase质子泵来执行其生物学活性。
DOI：
10.1038/s41598-021-90948-3
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发表时间：
2021-06-02
影响因子：
4.6
通讯作者：
Kannan TR
中科院分区：
文献类型：
--
作者：
Ramasamy K;Balasubramanian S;Kirkpatrick A;Szabo D;Pandranki L;Baseman JB;Kannan TR
肺炎支原体是美国住院儿童中细菌性社区获得性肺炎的主要原因。它也是儿童和成人的一系列其他呼吸道疾病和肺外表现的原因。M.肺炎链球菌是一种591个氨基酸的多功能蛋白质，称为社区获得性呼吸窘迫综合征（Community Acquired Respiratory Distress Syndrome，简称ARDS）毒素。该毒素的氨基端（N-Arg）保留ADP-核糖基化活性，羧基端（C-Arg）具有受体结合和空泡形成活性。内化后，肉毒毒素以逆行方式从内体通过高尔基复合体转运到内质网。然而，机制和标准，内化的肉毒毒素的运输和激活执行其细胞毒性作用仍然未知。在这项研究中，我们使用了全长肉毒毒素及其突变体和截短衍生物来分析药理学药物如何改变细胞内囊泡的pH值和跨囊泡膜的电位，影响肉毒毒素在哺乳动物细胞中的易位。我们的研究结果表明，酸性环境是必不可少的毒素逆行转运到内质网。此外，逆行运输促进毒素剪切，并需要诱导空泡形成。此外，毒素介导的细胞空泡化严格依赖于空泡型ATP酶的功能。
Mycoplasma pneumoniae is the leading cause of bacterial community-acquired pneumonia among hospitalized children in the United States. It is also responsible for a spectrum of other respiratory tract disorders and extrapulmonary manifestations in children and adults. The main virulence factor of M. pneumoniae is a 591 amino acid multifunctional protein called Community Acquired Respiratory Distress Syndrome (CARDS) toxin. The amino terminal region of CARDS toxin (N-CARDS) retains ADP-ribosylating activity and the carboxy region (C-CARDS) contains the receptor binding and vacuolating activities. After internalization, CARDS toxin is transported in a retrograde manner from endosome through the Golgi complex into the endoplasmic reticulum. However, the mechanisms and criteria by which internalized CARDS toxin is transported and activated to execute its cytotoxic effects remain unknown. In this study, we used full-length CARDS toxin and its mutant and truncated derivatives to analyze how pharmacological drugs that alter pH of intracellular vesicles and electrical potential across vesicular membranes affect translocation of CARDS toxin in mammalian cells. Our results indicate that an acidic environment is essential for CARDS toxin retrograde transport to endoplasmic reticulum. Moreover, retrograde transport facilitates toxin clipping and is required to induce vacuole formation. Additionally, toxin-mediated cell vacuolation is strictly dependent on the function of vacuolar type-ATPase.
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影响因子：
3.7
作者：
Johnson C;Kannan TR;Baseman JB
通讯作者：
Baseman JB
影响因子：
6.4
作者：
Bose S;Segovia JA;Somarajan SR;Chang TH;Kannan TR;Baseman JB
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Baseman JB
影响因子：
3.2
作者：
KIM, K;GROMAN, NB
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GROMAN, NB
影响因子：
7.8
作者：
GRIFFITHS, G;QUINN, P;WARREN, G
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影响因子：
3.4
作者：
Balasubramanian, Sowmya;Pandranki, Lavanya;Kannan, Thirumalai R.
通讯作者：
Kannan, Thirumalai R.