替拉扎明对多重耐药沙门菌抗菌增敏活性分析

Analysis of the Antibacterial Sensitization Activity of Tirapazamine against Multi-Drug Resistant Salmonella

本研究旨在探究替拉扎明对沙门菌的抗菌作用机制。通过药敏试验筛选3株多重耐药沙门菌,测定替拉扎明对多重耐药沙门菌的最小抑菌浓度(MIC)、最小杀菌浓度(MBC)、抗菌效果、时间杀菌曲线及生物被膜形成能力,并分析替拉扎明对沙门菌生长增殖、耐药表型和生物被膜形成的影响。结果表明,替拉扎明对多重耐药沙门菌有明显的抗菌作用,对沙门菌ST、ST-6和ST-7的MIC值分别为12.5、25、25μmol·L^(-1),MBC值均为50μmol·L^(-1)。随着替拉扎明作用浓度的增加和作用时间的延长,在共同培养4 h后明显抑制沙门菌的生长,50μmol·L^(-1)替拉扎明分别和沙门菌ST、ST-6和ST-7共培养8、20和20 h后,沙门菌被全部杀死;替拉扎明显著逆转多重耐药沙门菌的耐药表型;替拉扎明对沙门菌生物被膜的形成能力和形成量产生明显的抑制作用(P<0.0001)。替拉扎明对多重耐药沙门菌产生明显抗菌作用,且能逆转多重耐药表型和减少生物被膜的形成。研究结果阐明了替拉扎明对多重耐药沙门菌的抗菌活性,为治疗和控制由沙门菌感染引起的疾病提供新的治疗药物。

The aim of this study was to explore the antibacterial mechanism of tirapazamine(TPZ)on Salmonella.We screened three multi-drug resistant Salmonella strains through drug sensitivity test,and measured the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),antimicrobial antibacterial effect,time bactericidal curve and biofilm formation ability of TPZ against multi-drug resistant Salmonella.The growth and proliferation of TPZ on Salmonella,the effects of drug resistance phenotype and biofilm formation were analyzed.The results showed that TPZ had obvious antibacterial effect on multi-drug resistant Salmonella,and the MIC values respectively of Salmonella strains ST,ST-6 and ST-7 were 12.5,25 and 25μmol·L^(-1).MBC value was 50μmol·L^(-1).With the increases of the action concentration and prolongation of the action time of TPZ,the growth of Salmonella was significantly inhibited after co-culture for 4 hours,the cultivation of 50μmol·L^(-1)of TPZ was co-cultured with Salmonella ST,ST-6 and ST-7 for 8,20 and 20 h respectively,and all Salmonella was killed;TPZ significantly reversed the drug resistance phenotype of multi-drug resistant Salmonella;TPZ had a significant inhibitory effect on the formation ability and amount of Salmonella biofilm(P<0.0001).TPZ had obvious antibacterial effect on multi-drug resistant Salmonella,and it could reverse the multi-drug resistance phenotype and reduce the formation of biofilm.The results of the study elucidated the antibacterial activity of TPZ against multi-drug resistant Salmonella,and new therapeutic drugs had been provided for the treatment and control of infections caused by Salmonella infection.