Biogenic silver nanoparticle (Bio‐AgNP) has an antibacterial effect against carbapenem‐resistant Acinetobacter baumannii with synergism and additivity when combined with polymyxin B

Abstract

Carbapenem-resistant Acinetobacter baumannii represents a public health problem, and the search for new antibacterial drugs has become a priority. Here, we investigate the antibacterial activity of biogenic silver nanoparticles (Bio-AgNPs) synthesized by Fusarium oxysporum, used alone or in combination with polymyxin B against carbapenem-resistant A. baumannii. In this study, ATCC® 19606™ strain and four carbapenem-resistant A. baumannii strains were used. The antibacterial activity of Bio-AgNPs and its synergism with polymyxin B were determined using broth microdilution, checkboard methods and time-kill assays. The integrity of the bacterial cell membrane was monitored by protein leakage assay. In addition, the cytotoxicity in the VERO mammalian cell line was also evaluated, and the selectivity index was calculated. Bio-AgNPs have an antibacterial activity with MIC and MBC ranging from 0.460 to 1.870µg/ml. The combination of polymyxin B and Bio-AgNPs presents synergy against four of the five strains tested and additivity against one strain in the checkerboard assay. Considering the time of cell death, Bio-AgNPs killed all carbapenem-resistant isolates and ATCC® 19606™ within 1h. When combined, Bio-AgNPs presented 16-fold reduction of the polymyxin B MIC and showed a decrease in terms of viable A. baumannii cells in 4h of treatment, with synergic and additive effects. Protein leakage was observed with increasing concentrations for Bio-AgNPs treatments. Additionally, Bio-AgNP and polymyxin B showed dose-dependent cytotoxicity against mammalian VERO cells and combined the cytotoxicity which was significantly reduced and presented a greater pharmacological safety. The results presented here indicate that Bio-AgNPs in combination with polymyxin B could represent a good alternative in the treatment of carbapenem-resistant A. baumannii. This study demonstrates the synergic effect between Bio-AgNPs and polymyxin B on carbapenem-resistant A. baumannii strains.