Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC.
Pyroptosis of Salmonella Typhimurium-infected macrophages was suppressed and elimination of intracellular bacteria from macrophages was promoted by blocking QseC.
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通过阻断 QseC，鼠伤寒沙门氏菌感染的巨噬细胞的焦亡被抑制，并促进巨噬细胞内细菌的清除
DOI：
10.1038/srep37447
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发表时间：
2016-11-17
影响因子：
4.6
通讯作者：
Luo X
中科院分区：
文献类型：
--
作者：
Li Z;Zheng Q;Xue X;Shi X;Zhou Y;Da F;Qu D;Hou Z;Luo X
QseC是在革兰氏阴性病原体中发现的膜结合组氨酸传感器激酶，并且参与细菌毒力的调节。LED 209是一种QseC特异性抑制剂，可显著抑制几种病原体的毒力，并通过阻断QseC部分保护感染小鼠免于死亡。然而，其抗菌作用的机制仍不清楚。在本实验中，鼠伤寒沙门氏菌（S。鼠伤寒沙门氏菌）和巨噬细胞共培养系统来研究QseC抑制剂的抗微生物作用的潜在机制。QseC阻断抑制了S.鼠伤寒沙门氏菌，导致抑制病原体的游泳运动性、侵入能力和复制能力。乳酸脱氢酶（LDH）的释放。阻断QseC可显著抑制Typhimurium感染的巨噬细胞。在感染的巨噬细胞中，活化的caspase-1和IL-1β水平受到抑制，细胞内细菌计数减少。QseC阻断有效地降低了S.鼠伤寒沙门氏菌，抑制S。Typhimurium诱导巨噬细胞的细胞凋亡，并促进从感染的巨噬细胞中清除细胞内细菌。因此，QseC抑制剂的抗菌作用是通过增强S.巨噬细胞中的鼠伤寒。
QseC is a membrane-bound histidine sensor kinase found in Gram-negative pathogens and is involved in the regulation of bacterial virulence. LED209, a QseC-specific inhibitor, significantly inhibits the virulence of several pathogens and partially protects infected mice from death by blocking QseC. However, the mechanism of its antibacterial effects remains unclear. In this experiment, a Salmonella Typhimurium (S. Typhimurium) and macrophage co-culture system was utilized to investigate possible mechanisms underlying the antimicrobial effects of the QseC inhibitor. QseC blockade inhibited the expression of QseC-dependent virulence genes, including flhDC, sifA, and sopB, in S. Typhimurium, leading to inhibition of swimming motility, invasion capacity, and replication capacity of the pathogens. Release of lactate dehydrogenase (LDH) from S. Typhimurium-infected macrophages was significantly inhibited by blocking QseC. Activated caspase-1 and IL-1β levels were suppressed, and intracellular bacterial count was reduced in infected macrophages. QseC blockade effectively reduced the virulence of S. Typhimurium, inhibited S. Typhimurium-induced pyroptosis of macrophages, and promoted elimination of intracellular bacteria from infected macrophages. Thus, the antibacterial effects of QseC inhibitor are mediated via enhancement of intracellular killing of S. Typhimurium in macrophages.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.0913087107
发表时间：
2010-02-16
影响因子：
11.1
作者：
Miao, Edward A.;Mao, Dat P.;Aderem, Alan
通讯作者：
Aderem, Alan
影响因子：
6.9
作者：
Hawkey, P. M.
通讯作者：
Hawkey, P. M.
影响因子：
6.4
作者：
CANNON, JG;TOMPKINS, RG;DINARELLO, CA
通讯作者：
DINARELLO, CA
阻塞系统性炎症中的IL-1。
影响因子：
15.3
作者：
Dinarello, Charles A
通讯作者：
Dinarello, Charles A