Sub-Inhibitory Kanamycin Changes Outer Membrane Porin Ratios in Escherichia coli B23 by Increasing the Level of OmpC

Abstract

Previous studies have shown that E. coli B23 cells pretreated with a sub-inhibitory concentration of the aminoglycoside kanamycin develop short term (1.5 hour) resistance against lethal concentrations of tetracycline, ampicillin, streptomycin and kanamycin, as well as long term (24 hour) resistance to streptomycin and kanamycin. Modulation of outer membrane porins such as OmpC and OmpF has been suggested as an early line of defense to antibiotherapy by provoking a decrease in membrane permeability. Given that OmpC and OmpF have been shown to be important for the uptake of antibiotics for which cross-resistance was observed, this study isolated and quantified their expression in outer membrane extracts from E. coli B23 treated with sub-inhibitory kanamycin. It was observed that upon exposure to sub-inhibitory concentrations of kanamycin, OmpC levels increased relative to the OmpA, while OmpF levels did not, concordant with our expectations as OmpC is the smaller of the two porins and excludes the passage of larger hydrophilic antibiotics capable of permeating OmpF. The results of this study help to further elucidate the mechanism(s) of adaptive resistance observed in Escherichia coli B23 following exposure to sub-inhibitory concentrations of kanamycin.