Aguilar-Ayala Diana Angelica, Cnockaert Margo, Vandamme Peter, Palomino Juan Carlos, Martin Anandi, Gonzalez-Y-Merchand Jorge
Laboratory of Microbiology, Department of Biochemistry and Microbiology, Ghent University, Ghent 9000, Belgium.
Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, 11340, Mexico.
J Med Microbiol. 2018 Mar;67(3):282-285. doi: 10.1099/jmm.0.000681. Epub 2018 Jan 15.
Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model. Although their effectiveness in in vitro cultures with dextrose as a carbon source has been proved, we observed that none of the antibiotic mixtures were bactericidal in the presence of lipids. The presence of lipids may confer tolerance to M. tuberculosis against the mixture of antibiotics tested and such tolerance could be even higher during the dormant stages. The implementation of lipids in DST on clinical isolates could potentially lead to a better treatment strategy.
尽管结核病治疗依赖于药敏试验（DST）和分子耐药性检测，但治疗失败和复发仍然是一个挑战。这可能部分归因于抗生素耐受的休眠分枝杆菌的出现，其中宿主脂质已被证明发挥重要作用。本研究在富含脂质的休眠模型中评估了结核分枝杆菌对两种抗生素组合——利福平、莫西沙星、阿米卡星和甲硝唑（RIF-MXF-AMK-MTZ），以及利福平、莫西沙星、阿米卡星和普瑞玛尼（RIF-MXF-AMK-PA）——的敏感性。尽管它们在以葡萄糖作为碳源的体外培养中的有效性已得到证实，但我们观察到在脂质存在的情况下，没有一种抗生素混合物具有杀菌作用。脂质的存在可能使结核分枝杆菌对所测试的抗生素混合物产生耐受性，并且在休眠阶段这种耐受性可能更高。在临床分离株的药敏试验中加入脂质可能会带来更好的治疗策略。
