Antimicrobial effects of the anti-parasite drug flurlalner against Staphylococcus aureus
Objective This study aimed to investigate the antimicrobial effects of the anti-parasite drug fluralaner against Staphylococcus aureus.Methods S.aureus clinical isolates of SA 1901 and SA 1902 were collected from the thoracic fluid of pyothorax patients in May 2023.The antimicrobial susceptibility of fluralaner against S.aureus was determined by the micro-broth dilution assay and time-killing curves.The consecutive resistance-inducing assay was used to detect the resistance-inducing ability of fluralaner.The persister cell killing assay,the anti-biofilm assay and the laser confocal microscope were used to explore the anti-persister and anti-biofilm activities of fluralaner.Last,the combinational antimicrobial effects between fluralaner and aminoglycosides were determined by the checkerboard dilution assay.Results The minimal inhibitory concentration(MIC)and minimal bactericidal concentration of fluralaner against S.aureus were 4～8 μg/mL and 8～16 μg/mL,respectively.The sub-MIC of fluralaner was found to effectively inhibit bacterial growth by the time-killing assay.No resistant mutation was observed even after fluralaner treatment for 15 consecutive days.After 4 h treatment,8×MIC of fluralaner could significantly reduce the viable persister cells of ATCC 25923 and USA300 from(8.97±0.35)Log10 CFU/mL to(7.47±0.09)Log10 CFU/mL(t=7.17,P=0.002),and from(9.35±0.31)Log10 CFU/mL to(6.79±0.20)Log10 CFU/mL(t=12.04,P＜0.001),respectively.Fluralaner could significantly inhibit the biofilm formation of USA300 from(2.41±0.12)to(0.20±0.06)(t=44.03,P＜0.0001)at the concentration of 1×MIC;and 1×MIC of fluralaner could also significantly eradicate the pre-formed biofilm form(3.02±0.02)to(2.04±0.39)(t=5.58,P=0.0008);By checkerboard dilution assay and viable bacteria counting,amikacin was found to be synergistic with fluralaner against S.aureus with a synergistic antiacterial index of 0.375.Conclusion Fluralaner showed significant antimicrobial effects against S.aureus and could be synergistic with amikacin against S.aureus.
Staphylococcus aureusFluralanerPersister cellsBiofilmAntibiotic drug
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