The aim of this study was to test whether mannosylated BSA (Man-BSA) exerts antibacterial activity on Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria) via its membrane-damaging effect. Man-BSA caused inhibition of growth of E. coli and S. aureus. Moreover, bactericidal action of Man-BSA on E. coli and S. aureus positively correlated with the increase in membrane permeability of the bacterial cells. Morphological examination showed that Man-BSA disrupted bacterial membrane integrity. Destabilization of the lipopolysaccharide (LPS) layer and inhibition of lipoteichoic acid (LTA) biosynthesis in the cell wall increased the bactericidal effect of Man-BSA on E. coli and S. aureus. Man-BSA also induced leakage and fusion of membrane-mimicking liposomes in E. coli and S. aureus. Man-BSA showed similar binding affinity for LPS and LTA. LPS and LTA strongly suppressed the membrane-damaging activity of Man-BSA, whereas an increase in the Man-BSA concentration attenuated the inhibitory action of LPS and LTA. Taken together, our data indicate that Man-BSA's bactericidal activity depends strongly on its ability to induce membrane permeability. Moreover, the bactericidal action of Man-BSA proven in this study suggests that Man-BSA may serve as a prototype for the development of anti-infective agents targeting E. coli and S. aureus.
Keywords: Bactericidal effect; Fusogenicity; Mannosylated BSA; Membrane-damaging activity.
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