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Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases

Heesterbeek, DA; Bardoel, BW; Parsons, ES; Bennett, I; Ruyken, M; Doorduijn, DJ; Gorham, RD; ... Rooijakkers, SH; + view all (2019) Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases. EMBO Journal , Article e99852. 10.15252/embj.201899852. (In press). Green open access

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Abstract

The immune system kills bacteria by the formation of lytic membrane attack complexes (MACs), triggered when complement enzymes cleave C5. At present, it is not understood how the MAC perturbs the composite cell envelope of Gram-negative bacteria. Here, we show that the role of C5 convertase enzymes in MAC assembly extends beyond the cleavage of C5 into the MAC precursor C5b. Although purified MAC complexes generated from preassembled C5b6 perforate artificial lipid membranes and mammalian cells, these components lack bactericidal activity. In order to permeabilize both the bacterial outer and inner membrane and thus kill a bacterium, MACs need to be assembled locally by the C5 convertase enzymes. Our data indicate that C5b6 rapidly loses the capacity to form bactericidal pores; therefore, bacterial killing requires both in situ conversion of C5 and immediate insertion of C5b67 into the membrane. Using flow cytometry and atomic force microscopy, we show that local assembly of C5b6 at the bacterial surface is required for the efficient insertion of MAC pores into bacterial membranes. These studies provide basic molecular insights into MAC assembly and bacterial killing by the immune system.

Type: Article
Title: Bacterial killing by complement requires membrane attack complex formation via surface-bound C5 convertases
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.15252/embj.201899852
Publisher version: https://doi.org/10.15252/embj.201899852
Language: English
Additional information: © 2019 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/
Keywords: Gram‐negative bacteria, atomic force microscopy, complement; convertase, membrane attack complex
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Physics and Astronomy
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology
URI: http://discovery.ucl.ac.uk/id/eprint/10067179
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