In vitro and in vivo synergistic effect of chrysin in combination with colistin against Acinetobacter baumannii

Abstract

Acinetobacter baumannii is an opportunistic pathogen that is primarily associated with nosocomial infections. With the rise in cases of acquired drug resistance, A. baumannii is gaining resistance to conventional antimicrobial drugs and even to the last line of antibiotics, such as colistin. Hence, the application of the synergistic combination of an antibiotic and a non-antibacterial agent is being contemplated as a new alternative therapeutic approach. Chrysin is a component of honey with anti-inflammatory and antioxidant properties. In this study, we evaluated the antibacterial activity of chrysin in combination with colistin against A. baumannii both in vitro and in vivo, as well as the cytotoxicity of chrysin with or without colistin. Our results revealed that chrysin and colistin exerted synergistic effects against A. baumannii by damaging the extracellular membrane and modifying the bacterial membrane potential. The chrysin/colistin combination group demonstrated an inhibitory effect on biofilm formation. In conclusion, it is expected that the synergy between these drugs can allow the use of a lower concentration of colistin for the treatment of A. baumannii infections, thereby reducing dose-dependent side effects. Thus, a combination therapy of chrysin/colistin may provide a new therapeutic option for controlling A. baumannii infections.

Flufenamic Acid, a Promising Agent for the Sensitization of Colistin-Resistant Gram-Negative Bacteria to Colistin

“…Cytotoxicity analyses also confirmed the excellent biosafety profile of this combination treatment regimen. Analyses of the potential mechanism of action whereby FFA sensitizes cells to colistin were performed using membrane permeability assays with propidium iodide (PI), which showed that FFA may induce damage to the bacterial membrane, thereby enhancing the antibacterial efficacy of colistin ( 31 – 33 ). These findings demonstrated the potential of this combination for in vivo use in the future.…”

Azomycin Orchestrate Colistin-Resistant Enterobacter cloacae Complex’s Colistin Resistance Reversal In Vitro and In Vivo

“…The safety of azomycin and azomycin–colistin was evaluated using the RBC hemolysis test and cytotoxicity test . Briefly, erythrocytes collected from healthy male mice were used to prepare a 5% erythrocyte suspension with PBS.…”

“…The safety of azomycin and azomycin−colistin was evaluated using the RBC hemolysis test 34 and cytotoxicity test. 35 Briefly, erythrocytes collected from healthy male mice were used to prepare a 5% erythrocyte suspension with PBS. Azomycin (1 to 64 μg/mL) was added for the experimental group, whereas DMSO (1−5%) was added for the solvent control group.…”

“…Bacterial load was quantified by counting cfu after spotting on agar plates. 35 Quantitative Test for Reactive Oxygen Species. To assess the generation of ROS under different treatment conditions, the following experimental operations was employed.…”

“…Data were normalized to rpoB expression, which was used as a reference housekeeping gene. 25,35 Multipassage Assay. The multipassage assay was performed as described, 26 with some modifications.…”