Vocat Anthony, Luraschi-Eggemann Amanda, Antoni Claudia, Cathomen Gino, Cichocka Danuta, Greub Gilbert, Riabova Olga, Makarov Vadim, Opota Onya, Mendoza Alfonso, Cole Stewart T, Sturm Alexander
Resistell AG, Muttenz, Switzerland.
Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Antimicrob Agents Chemother. 2025 Jan 31;69(1):e0131824. doi: 10.1128/aac.01318-24. Epub 2024 Nov 27.
Novel drugs and improved diagnostics for (MTB) are urgently needed and go hand in hand. We evaluated the activity of two benzothiazinone drug candidates (MCZ, PBTZ169; BTZ043) and their main metabolites against MTB using advanced nanomotion technology. The results demonstrated significant reductions in MTB viability within 7 h, indicating the potential for rapid, precise antibiotic susceptibility testing based on a phenotypic read-out in real time. PBTZ169 and H-PBTZ169 achieved 100% separation between the susceptible H37Rv and a resistant mutant strain NTB1. These findings support nanomotion technology's potential for faster antibiotic susceptibility testing of novel MTB drug candidates targeting the DprE1 enzyme that could reduce empirical treatment duration and antibiotic resistance selection pressure due to inaccurate treatments.
迫切需要新型药物和改进的诊断方法来应对结核分枝杆菌（MTB），二者相辅相成。我们使用先进的纳米运动技术评估了两种苯并噻嗪酮候选药物（MCZ、PBTZ169；BTZ043）及其主要代谢产物对MTB的活性。结果表明，在7小时内MTB活力显著降低，这表明基于实时表型读数进行快速、精确的抗生素敏感性测试具有潜力。PBTZ169和H-PBTZ169在敏感的H37Rv和耐药突变菌株NTB1之间实现了100%的区分。这些发现支持了纳米运动技术在针对DprE1酶的新型MTB候选药物的更快抗生素敏感性测试方面的潜力，这可能会减少经验性治疗时间以及不准确治疗导致的抗生素耐药性选择压力。
