Antibody-independent interaction between the first component of human complement, C1, and the outer membrane of Escherichia coli D31 m4

Abstract

The heptoseless mutant of Escherichia coli, E. coli D31 m4, binds C1q and C1 at 0 degrees C and at low ionic strength (I0.07). Under these conditions, the maximum C1q binding averages 3.0 X 10(5) molecules per bacterium, with a Ka of 1.4 X 10(8) M-1. Binding involves the collagen-like region of C1q, as shown by the capacity of C1q pepsin-digest fragments to bind to E. coli D31 m4, and to compete with native C1q. Proenzyme and activated forms of C1 subcomponents C1r and C1s and their Ca2+-dependent association (C1r-C1s)2 do not bind to E. coli D31 m4. In contrast, the C1 complex binds very effectively, with an average fixation of 3.5 X 10(5) molecules per bacterium, and a Ka of 0.25 X 10(8) M-1, both comparable with the values obtained for C1q binding. C1 bound to E. coli D31 m4 undergoes rapid activation at 0 degrees C. The activation process is not affected by C1-inhibitor, and only slightly inhibited by p-nitrophenyl p'-guanidinobenzoate. No turnover of the (C1r-C1s)2 subunit is observed. Once activated, C1 is only partially dissociated by C1-inhibitor. Our observations are in favour of a strong association between C1 and the outer membrane of E. coli D31 m4, involving mainly the collagen-like moiety of C1.

An Alternative Role of C1q in Bacterial Infections: FacilitatingStreptococcus pneumoniaeAdherence and Invasion of Host Cells

“…Although, a number of C1q ligands have been characterized on apoptotic cells, the list is relatively short in the case of bacterial pathogens. The only reported bacterial ligand of C1q is the OmpK36 porin of K. pneumoniae (20), whereas still uncharacterized outer membrane proteins have been suggested to be the ligands for other bacterial species (16,17,19,21,22). In accordance, in this study, we showed that C1q interacts via its C-terminal globular heads primarily with the pneumococcal surface-exposed protein(s).…”

“…There have been reports describing direct binding of C1q to pathogens, independent of the presence of recognizing Abs or other ligands (16)(17)(18)(19)(20)(21)(22). Accordingly, direct and Ab-independent binding of C1q was observed for clinical isolates of E. coli, S. pyogenes, M. catarrhalis, and nontypeable H. influenzae.…”

“…The direct activation of the classical pathway by pneumococci is not unique, as direct and Ab-independent binding of C1q was demonstrated also for group B streptococci (16), Salmonella minnesota (17), Escherichia coli (18,19), Klebsiella pneumoniae (20), Legionella pneumophila (21), and Streptococcus pyogenes (22). In this study, we have investigated the Ab-independent binding of C1q to the respiratory tract pathogen S. pneumoniae.…”

Bacteria microarrays as sensitive tools for exploring pathogen surface epitopes and recognition by host receptors

“…Lipopolysaccharides and outer-membrane proteins of the porin class are examples of molecules targeted by C1q. [45][46][47] Furthermore, some bacteria, such as Escherichia coli or P. aeruginosa, express a specic receptor for C1q aimed to protect them from complement-mediated damage. 48 Regarding K. pneumoniae, in vivo binding of C1q to porin OmpK36, present in most clinical isolates including the Kp52145 strain used in this work, has been reported, whereas binding to other components of the bacterial outer membrane, in particular the lipopolysaccharide lacking OPS could not be demonstrated.…”

Interaction of Neisseria gonorrhoeae with classical complement components, C1-inhibitor, and a monoclonal antibody directed against the Neisserial H.8 antigen.

“…Selected mutants of gram-negative enteric organisms directly activate the classical complement pathway in vitro in the absence ofantibody (6)(7)(8)(9). The initiating event is conversion of zymogen Cl to its active serine esterase form (reviewed in references 10 and I 1) upon interaction ofCl with constituents of the bacterial outer membrane.…”