Complement-mediated killing of bacteria by mechanical destabilization of the cell envelope

Complement-mediated killing of bacteria by mechanical destabilization of the cell envelope
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通过细胞膜的机械不稳定来补体介导的细菌杀灭

DOI:
10.1101/2023.12.10.570986
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发表时间:
2023
期刊:
--
影响因子:
--
通讯作者:
Benn G
Benn G
中科院分区:
--
文献类型:
--
作者:
Benn G

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补体蛋白通过在外膜形成膜攻击复合体(MAC)孔来消除血清中的革兰氏阴性菌。然而,外膜穿孔如何导致内膜渗透和细胞溶解仍不清楚。利用原子力显微镜(AFM)对活的大肠杆菌(E.coli)进行研究,探讨了MAC诱导的细胞膜的变化,并将这些变化与随后的细胞死亡联系起来。最初,尽管细胞表面随机分布着数百个Mac,细菌还是存活了下来。紧随其后的是外膜的更大范围的破坏,包括传播的缺陷和断裂,以及细菌表面的整体肿胀和僵硬,这在内膜渗透之前。我们的结论是,细菌细胞裂解只是MAC形成的间接影响;外膜穿孔导致细胞被膜机械失稳,降低其控制膨胀压力的能力,导致内膜渗透和细胞死亡。这代表了一种以前未知的导致细菌细胞死亡的途径,可以被新的抗生素治疗方法所利用。
Complement proteins eliminate Gram-negative bacteria in serum via the formation of membrane attack complex (MAC) pores in the outer membrane. However, it remains unclear how outer membrane poration leads to inner membrane permeation and cell lysis. Using atomic force microscopy (AFM) on livingEscherichia coli(E. coli), we probed MAC-induced changes in the cell envelope and correlated these with subsequent cell death. Initially, bacteria survived despite the formation of hundreds of MACs randomly distributed over the cell surface. This was followed by larger-scale disruption of the outer membrane, including propagating defects and fractures, and by an overall swelling and stiffening of the bacterial surface, which precede inner membrane permeation. We conclude that bacterial cell lysis is only an indirect effect of MAC formation; outer membrane poration leads to mechanical destabilization of the cell envelope, reducing its ability to contain the turgor pressure, causing inner membrane permeation and cell death. This represents a previously unknown route to bacterial cell death that could be exploited by novel antibiotic treatments.
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