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Bacterial killing by complement requires membrane attack complex formation via surface‐bound C5 convertases
Author(s) -
Heesterbeek Dani AC,
Bardoel Bart W,
Parsons Edward S,
Bennett Isabel,
Ruyken Maartje,
Doorduijn Dennis J,
Gorham Ronald D,
Berends Evelien TM,
Pyne Alice LB,
Hoogenboom Bart W,
Rooijakkers Suzan HM
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899852
Subject(s) - clinical microbiology , university hospital , library science , medical school , medicine , biology , microbiology and biotechnology , family medicine , computer science , medical education
The immune system kills bacteria by the formation of lytic membrane attack complexes ( MAC s), 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, MAC s 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.