Bacterial Membrane Destabilization with Cationic Particles of Nano-silver to Combat Efflux-mediated Antibiotic Resistance in Gram-negative Bacteria

Aims: With the purpose of exploring combinatorial options that could enhance the bactericide efficacy of linezolid against Gram-negative bacteria, we assessed the extent of combination of nano-silver and linezolid.

Main Methods: In this study, we selected Escherichia coli MTCC 443 as a model to study the combinatorial effect of nano-silver and linezolid to combat efflux-mediated resistance in Gram-negative bacteria. The acting mechanism of nano-silver on E. coli MTCC 443 was investigated by evaluating interaction of nano-silver with bacterial membrane as well as bacterial surface charge, morphology, intracellular leakages and biological activities of membrane bound respiratory chain dehydrogenase and deoxyribonucleic acids (DNA) of the cells following treatment with nano-silver.

Key Findings: The alternation of zeta potential due to the interaction of nano-silver towards bacterial membrane proteins was correlated with enhancement of membrane permeability, which allows the penetration of linezolid into the cells. In addition, the binding affinity of nano-silver towards bacterial membrane depressed biological activities of membrane bound respiratory chain dehydrogenases and DNA integrity.

Significance: Our findings suggested that nano-silver could not only obstruct the activities of efflux pumps, but also altered membrane integrity at the same time and thus increased the cytoplasmic concentration of the linezolid to the effective level.