PDF(Pubmed)
Abstract：
Neisseria gonorrhoeae has developed resistance to every antibiotic currently approved for the treatment of gonorrhea, prompting the development of new therapies. The phenoxazine dye resazurin exhibits robust antimicrobial activity against N. gonorrhoeae in vitro but fails to limit vaginal colonization by N. gonorrhoeae in a mouse model. The lack of in vivo efficacy may be due to oxygen limitation as in vitro susceptibility assays with resazurin are conducted under atmospheric oxygen while a microaerophilic environment is present in the vagina. Here, we utilized broth microdilution assays to determine the susceptibility of N. gonorrhoeae to resazurin under low and atmospheric oxygen conditions. The minimal inhibitory concentration of resazurin for multiple N. gonorrhoeae clinical isolates was significantly higher under low oxygen. This effect was specific to resazurin as N. gonorrhoeae was equally susceptible to other antibiotics under low and atmospheric oxygen conditions. The reduced susceptibility of N. gonorrhoeae to resazurin under low oxygen was largely attributed to reduced oxidative stress, as the addition of antioxidants under atmospheric oxygen mimicked the reduced susceptibility to resazurin observed under low oxygen. Together, these data suggest oxygen concentration is an important factor to consider when evaluating the efficacy of new antibiotics against N. gonorrhoeae in vitro.
摘要：
淋病奈瑟菌对目前批准用于治疗淋病的每一种抗生素都产生了耐药性，促使新疗法的发展。吩恶嗪染料刃天青在体外对淋病奈瑟菌表现出强大的抗微生物活性，但在小鼠模型中不能限制淋病奈瑟菌的阴道定植。体内功效的缺乏可能是由于氧的限制，因为在阴道中存在微需氧环境的同时，在大气氧气下进行了刃天青的体外敏感性测定。这里,我们利用肉汤微量稀释试验来确定在低氧和大气氧条件下淋病奈瑟菌对白天灵的敏感性。在低氧条件下，对多个淋病奈瑟菌临床分离株的刃天青的最低抑制浓度明显较高。这种作用是riazurin特有的，因为淋病奈瑟菌在低氧和大气氧条件下同样容易受到其他抗生素的影响。在低氧条件下，淋病奈瑟菌对白天青的敏感性降低主要归因于氧化应激的降低。由于在大气氧气下添加抗氧化剂模拟了在低氧下观察到的对刀天青的敏感性降低。一起,这些数据表明,在体外评价新型抗生素对淋病奈瑟菌的疗效时,氧浓度是一个需要考虑的重要因素.
