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

Autor:	Heesterbeek DA; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Bardoel BW; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Parsons ES; London Centre for Nanotechnology, University College London, London, UK., Bennett I; London Centre for Nanotechnology, University College London, London, UK., Ruyken M; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Doorduijn DJ; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Gorham RD Jr; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Berends ET; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Pyne AL; London Centre for Nanotechnology, University College London, London, UK., Hoogenboom BW; London Centre for Nanotechnology, University College London, London, UK.; Department of Physics and Astronomy, University College London, London, UK., Rooijakkers SH; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands s.h.m.rooijakkers@umcutrecht.nl.
Jazyk:	angličtina
Zdroj:	The EMBO journal [EMBO J] 2019 Feb 15; Vol. 38 (4). Date of Electronic Publication: 2019 Jan 14.
DOI:	10.15252/embj.201899852
Abstrakt:	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. (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze:	MEDLINE
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