Antibacterial and membrane-damaging activities of mannosylated bovine serum albumin

Arch Biochem Biophys. 2015 May 1:573:14-22. doi: 10.1016/j.abb.2015.02.034. Epub 2015 Mar 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Membrane Permeability
  • Cell Wall / drug effects
  • Cell Wall / metabolism
  • Escherichia coli / drug effects
  • Humans
  • Lipopolysaccharides / pharmacology
  • Mannose / pharmacology*
  • Serum Albumin / pharmacology*
  • Staphylococcus aureus / drug effects
  • Teichoic Acids / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Bacterial Agents
  • Lipopolysaccharides
  • Serum Albumin
  • Teichoic Acids
  • Tumor Necrosis Factor-alpha
  • mannose-bovine serum albumin conjugate
  • lipoteichoic acid
  • Mannose