Differences in Complement Activation Between Complement-resistant and Complement-sensitive Moraxella (Branhamella) Catarrhalis Strains Occur at the Level of Membrane Attack Complex Formation
Overview
Affiliations
The mechanism of resistance to human complement-mediated killing in Moraxella catarrhalis was studied by comparing different complement-sensitive and complement-resistant M. catarrhalis strains in a functional bystander hemolysis assay and an enzyme-linked immunosorbent assay (ELISA) for soluble terminal complement complexes. Complement-resistant stains appeared to activate complement to the same extent as, or even slightly better than, complement-sensitive strains. This indicates that complement-resistant strains do not inhibit classical or alternative pathway activation but interfere with complement at the level of membrane attack complex formation. A clear difference in dose-response curves for resistant and sensitive strains was observed both in the bystander hemolysis assay and in the ELISA. Complement-resistant strains showed optimum curves, whereas complement-sensitive strains gave almost linear curves. We conclude that resistant strains bind and/or inactivate one of the terminal complement components or intermediates involved in membrane attack complex formation. Trypsin, known to abolish complement resistance, changed the optimum dose-response curve of a resistant strain to a linear one, which strongly suggests that complement resistance is mediated by an M. catarrhalis-associated protein. This protein acts directly or through the binding of a terminal complement inhibitor present in serum.
Doorduijn D, Lukassen M, van t Wout M, Franc V, Ruyken M, Bardoel B Elife. 2022; 11.
PMID: 35947526 PMC: 9402229. DOI: 10.7554/eLife.77503.
Ariff A, Wise M, Kahler C, Tay C, Peters F, Perkins T BMC Genomics. 2015; 16:860.
PMID: 26497500 PMC: 4619438. DOI: 10.1186/s12864-015-2104-1.
Molecular aspects of Moraxella catarrhalis pathogenesis.
de Vries S, Bootsma H, Hays J, Hermans P Microbiol Mol Biol Rev. 2009; 73(3):389-406, Table of Contents.
PMID: 19721084 PMC: 2738133. DOI: 10.1128/MMBR.00007-09.
Attia A, Ram S, Rice P, Hansen E Infect Immun. 2006; 74(3):1597-611.
PMID: 16495531 PMC: 1418666. DOI: 10.1128/IAI.74.3.1597-1611.2006.
Attia A, Lafontaine E, Latimer J, Aebi C, Syrogiannopoulos G, Hansen E Infect Immun. 2005; 73(4):2400-10.
PMID: 15784586 PMC: 1087425. DOI: 10.1128/IAI.73.4.2400-2410.2005.