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抗菌肽藥物與羰基氰化物間氯苯腙對多重抗藥性鮑氏不動桿菌臨床分離株的協同作用研究

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抗菌肽藥物與羰基氰化物間氯苯腙對多重抗藥性鮑氏不動桿菌臨床分離株的協同作用研究

The synergistic action of antimicrobial peptides and carbonyl cyanide m-chlorophenyl hydrazone (CCCP) against multidrug resistant Acinetobacter baumannii clinical isolates

Abstract
Background & Objective: Acinetobacter baumannii is a ubiquitous Gram-negative bacterium that has been recognized as an opportunistic pathogen that is the most common bacterium associated with nosocomial infections. Infection with multi-drug resistance (MDR) A. baumannii is very difficult to treat. Antimicrobial peptides (AMPs) are short and mostly positively charged peptides widely found in many organisms. These cationic AMPs can bind and interact with negatively charged bacterial cell membranes, causing changes in the electrochemical potential on the bacterial cell membranes and increase the permeability of cell membranes. The purpose of this study was to evaluate the antibacterial activity of AMPs (colistin, polymyxin, poly-L-lysine and ε-poly-L-lysine) could be enhanced by an efflux inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP) against 10 MDR A.baumannii clinical isolates and one reference strain (ATCC 19606).
Method: Broth microdilution assay was used to investigate the antibacterial activity of the AMPs and CCCP. The potential synergistic activity of combined use of AMPs and CCCP was determined by checkerboard methods. Crystal violet staining was applied to determine bacterial biofilm formation.
Results: Our results showed the combination of AMPs with sub-MIC of CCCP (0.1~3 mM) showed synergistic bactericidal activity (FICI: 0.18~0.38) against 10~8 of 10 MDR A. baumannii clinical isolate. Compared with those of the CCCP-treated and polymyxin B-treated bacteria, the combination of CCCP (0.13mM) with polymyxin B (1~2 μg/mL) significantly inhibited biofilm formation and motility of two MDR A. baumannii strains. Results of growth inhibition assays also supported the synergistic effects of CCCP with polymyxin B against MDR A. baumannii clinical isolates.
Conclusion: Our results suggest the bactericidal activity of AMPs could be potentiated by the use of efflux inhibitors against MDR A. baumannii.

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