Effects of Sub-Minimal Inhibitory Concentrations of Antimicrobial Agents on the Cell Surface of Klebsiella pneumoniae and Phagocytic Killing Activity

Abstract

Changes in the phagocytic killing activity, capsule structure, and physicochemical properties such as the hydrophobicity and charge of the cell surface were studied in Klebsiella pneumoniae treated with sub-minimal inhibitory concentrations (MICs) of various antimicrobial agents. The phagocytic killing activity of macrophages was enhanced by penicillins, cephems, and monobactam in the absence of antibodies specific to the capsule or complement. No enhancement was observed with new quinolones, aminoglycosides, macrolide, or car-bapenem. The thickness of the capsule structure was considerably reduced after the treatment with penicillins, cephems, and monobactam compared with the untreated control, and it was slightly reduced by new quinolones. No changes were observed in the capsule structure with aminoglycosides, macrolide, and carbapenem. The hydrophobicity on the cell surface of the bacteria was considerably increased after the treatment with penicillins, cephems, and monobactam compared with the control, slightly increased with new quinolones and carbapenem, and not changed with aminoglycosides and macrolide. The negative charge of the cell surface of the bacteria was reduced by penicillins, cephems, and monobactam compared with the control. It was slightly reduced by new quinolones and carbapenem but was not reduced by aminoglycosides and macrolide. These findings suggest that sub-MIC beta-lactam drugs such as penicillins, cephems, and monobactams cause thinning of the capsule of K. pneumoniae with increases in the hydrophobicity and decreases in the negative charge of the cell surface, which reduces the physical repulsion between the K. pneumoniae and phagocytes and enhances the sensitivity of the bacteria to phagocytic killing activity.