The Importance of Porins and beta-Lactamase in Outer Membrane Vesicles on the Hydrolysis of beta-Lactam Antibiotics

Abstract

Gram-negative bacteria have an outer membrane inhibiting the entry of antibiotics. Porins, found within the outer membrane, are involved in regulating the permeability of beta-lactam antibiotics. beta-lactamases are enzymes that are able to inactivate the antibacterial properties of beta-lactam antibiotics. Interestingly, porins and beta-lactamase are found in outer membrane vesicles (OMVs) of beta-lactam-resistant Escherichia coli and may be involved in the survival of susceptible strains of E. coli in the presence of antibiotics, through the hydrolysis of the beta-lactam antibiotic. In this study, OMVs isolated from beta-lactam-resistant E. coli and from mutants, lacking porin or beta-lactamase, were evaluated to establish if the porins or beta-lactamase in OMVs were involved in the degradation of beta-lactam antibiotics. OMVs isolated from E. coli deficient in beta-lactamase did not show any degradation ability against beta-lactam antibiotics, while OMVs lacking OmpC or OmpF showed significantly lower levels of hydrolyzing activity than OMVs from parent E. coli. These data reveal an important role of OMVs in bacterial defense mechanisms demonstrating that the OmpC and OmpF proteins allow permeation of beta-lactam antibiotics into the lumen of OMVs, and antibiotics that enter the OMVs can be degraded by beta-lactamase.