[Background] Due to the abuse of antibiotics, bacterial drug resistance has become a severe problem. Therefore, it is urgent to find useful strategies to solve the current situation of drug-resistant bacterial infections. In clinical, the combination of Chinese medicine and antibiotics is significantly effective in preventing drug-resistant bacterial infections. [Objective] To study the synergistic effect of carvacrol combined with ceftriaxone on drug-resistant Salmonella (SJ2) and the mechanism. [Methods] The minimum antibacterial concentration (minimal inhibitory concentration, MIC) of carvacrol and ceftriaxone on SJ2 was determined by broth microdilution method. The activity of carvacrol combined with ceftriaxone against SJ2 was determined by checkerboard method and growth curve. The effects of carvacrol combined with ceftriaxone on SJ2 cell wall and membrane were studied by membrane potential detection, extracellular alkaline phosphatase (alkaline phosphatase, AKP) content determination, antibiotic accumulation analysis in bacteria, bacterial viability determination, and scanning electron microscopy. [Results] The MIC of carvacrol and ceftriaxone against SJ2 was 256 μg/mL and 2 048 μg/mL, respectively. The carvacrol and ceftriaxone had the synergistic effect on SJ2, and their fractional inhibitory concentration index (fractional inhibitory concentration index, FICI) was 0.375. Carvacrol combined with ceftriaxone depolarized the SJ2 cell membranes, and significantly increased the amount of extracellular AKP (P<0.05), the intracellular antibiotic accumulation (P<0.01), and the number of bacteria that disrupted cell membrane integrity and caused serious damage of structure. [Conclusion] Carvacrol combined with ceftriaxone has the synergistic effect against SJ2, and the synergistic mechanism can be realized by damaging the bacterial cell wall and cell membrane.
TANG Ting, YIN Lizi, ZHAO Sumei, DU Juan, HE Changliang. In vitro antimicrobial effects of carvacrol combined with ceftriaxone on drug-resistant Salmonella[J]. Microbiology China, 2023, 50(2): 573-583
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