DST-NRF Centre of Excellence in Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
Barcelona Biomedical Research Park, Centre for Genomic Regulation, Biomolecular Screening and Protein Technologies Unit, Barcelona, Spain.
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.02236-17. Print 2018 Apr.
The high acquisition rate of drug resistance by necessitates the ongoing search for new drugs to be incorporated in the tuberculosis (TB) regimen. Compounds used for the treatment of other diseases have the potential to be repurposed for the treatment of TB. In this study, a high-throughput screening of compounds against thiol-deficient strains and subsequent validation with thiol-deficient strains revealed that and mutants had increased susceptibility to azaguanine (Aza) and sulfaguanidine (Su); and mutants had increased susceptibility to bacitracin (Ba); and , , and mutants had increased susceptibility to fusaric acid (Fu). Further analyses revealed that some of these compounds were able to modulate the levels of thiols and oxidative stress in This study reports the activities of Aza, Su, Fu, and Ba against and provides a rationale for further investigations.
由于结核分枝杆菌（Mycobacterium tuberculosis）耐药性的高获得率，因此需要不断寻找新的药物来纳入结核病（TB）的治疗方案。用于治疗其他疾病的化合物有可能被重新用于治疗结核病。在这项研究中，对含巯基缺陷型结核分枝杆菌菌株进行了高通量化合物筛选，并用含巯基缺陷型结核分枝杆菌菌株进行了后续验证，结果表明，鸟嘌呤（Aza）和磺胺胍（Su）对缺失突变体和缺失突变体的敏感性增加；杆菌肽（Ba）对缺失突变体和缺失突变体的敏感性增加；黄曲霉酸（Fu）对缺失突变体、缺失突变体和缺失突变体的敏感性增加。进一步的分析表明，这些化合物中的一些能够调节结核分枝杆菌中巯基和氧化应激的水平。本研究报告了 Aza、Su、Fu 和 Ba 对结核分枝杆菌和的活性，并为进一步的研究提供了依据。
