Loss of Outer Membrane Protein C in Escherichia coli Contributes to Both Antibiotic Resistance and Escaping Antibody-Dependent Bactericidal Activity

Abstract

ABSTRACTOuter membrane proteins (OMPs) serve as the permeability channels for nutrients, toxins, and antibiotics. InEscherichia coli, OmpA has been shown to be involved in bacterial virulence, and OmpC is related to multidrug resistance. However, it is unclear whether OmpC also has a role in the virulence ofE. coli. The aims of this study were to characterize the role of OmpC in antimicrobial resistance and bacterial virulence inE. coli. TheompCdeletion mutant showed significantly decreased susceptibility to carbapenems and cefepime. To investigate the survival ofE. coliexposed to the innate immune system, a human blood bactericidal assay showed that theompCmutant increased survival in blood and serum but not in complement-inactivated serum. These effects were also demonstrated in the natural selection of OmpC mutants. Also, C1q interacted withE. colithrough a complex of antibodies bound to OmpC as a major target. Bacterial survival was increased in the wild-type strain in a dose-dependent manner by adding free recombinant OmpC protein or anti-C1q antibody to human serum. These results demonstrated that the interaction of OmpC-specific antibody and C1q was the key step in initiating the antibody-dependent classical pathway for the clearance of OmpC-expressingE. coli. Anti-OmpC antibody was detected in human sera, indicating that OmpC is an immunogen. These data indicate that the loss of OmpC inE. coliis resistant to not only antibiotics, but also the serum bactericidal effect, which is mediated from the C1q and anti-OmpC antibody-dependent classical pathway.