Benn Georgina, Bortolini Christian, Roberts David M, Pyne Alice L B, Holden Séamus, Hoogenboom Bart W
London Centre for Nanotechnology, University College London, London, WC1H 0AH, UK.
Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA.
EMBO J. 2024 Dec;43(23):6152-6160. doi: 10.1038/s44318-024-00266-3. Epub 2024 Oct 14.
Complement proteins eliminate Gram-negative bacteria in the blood 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 living Escherichia 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 that were 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, leading to inner membrane permeation and cell death.
补体蛋白通过在外膜形成膜攻击复合物（MAC）孔来清除血液中的革兰氏阴性细菌。然而，外膜成孔如何导致内膜渗透和细胞裂解仍不清楚。我们利用原子力显微镜（AFM）对活的大肠杆菌进行研究，探测MAC诱导的细胞包膜变化，并将这些变化与随后的细胞死亡相关联。最初，尽管在细胞表面随机形成了数百个MAC，细菌仍能存活。随后外膜出现更大规模的破坏，包括扩展的缺陷和破裂，以及细菌表面整体肿胀和变硬，这些都先于内膜渗透。我们得出结论，细菌细胞裂解只是MAC形成的间接效应；外膜成孔导致细胞包膜的机械不稳定，降低其容纳膨压的能力，从而导致内膜渗透和细胞死亡。
