Real-time evaluation of macozinone activity against Mycobacterium tuberculosis through bacterial nanomotion analysis.

IF 4.1 2区医学 Q2 MICROBIOLOGY

Antimicrobial Agents and Chemotherapy Pub Date : 2024-11-27 DOI:10.1128/aac.01318-24

Anthony Vocat, Amanda Luraschi-Eggemann, Claudia Antoni, Gino Cathomen, Danuta Cichocka, Gilbert Greub, Olga Riabova, Vadim Makarov, Onya Opota, Alfonso Mendoza, Stewart T Cole, Alexander Sturm

{"title":"Real-time evaluation of macozinone activity against Mycobacterium tuberculosis through bacterial nanomotion analysis.","authors":"Anthony Vocat, Amanda Luraschi-Eggemann, Claudia Antoni, Gino Cathomen, Danuta Cichocka, Gilbert Greub, Olga Riabova, Vadim Makarov, Onya Opota, Alfonso Mendoza, Stewart T Cole, Alexander Sturm","doi":"10.1128/aac.01318-24","DOIUrl":null,"url":null,"abstract":"Novel drugs and improved diagnostics for Mycobacterium tuberculosis (MTB) are urgently needed and go hand in hand. We evaluated the in vitro 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 H2-PBTZ169 achieved 100% separation between the susceptible H37Rv and a resistant dprE1 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.","PeriodicalId":8152,"journal":{"name":"Antimicrobial Agents and Chemotherapy","volume":" ","pages":"e0131824"},"PeriodicalIF":4.1000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antimicrobial Agents and Chemotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1128/aac.01318-24","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Novel drugs and improved diagnostics for Mycobacterium tuberculosis (MTB) are urgently needed and go hand in hand. We evaluated the in vitro 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 H₂-PBTZ169 achieved 100% separation between the susceptible H37Rv and a resistant dprE1 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.

查看原文本刊更多论文

通过细菌纳米运动分析实时评估马可西酮对结核分枝杆菌的活性。

结核分枝杆菌（MTB）急需新型药物和改进的诊断方法。我们利用先进的纳米技术评估了两种苯并噻嗪酮类候选药物（MCZ、PBTZ169；BTZ043）及其主要代谢物对 MTB 的体外活性。结果表明，在 7 小时内 MTB 的存活率明显降低，这表明基于表型实时读出的快速、精确抗生素药敏试验具有潜力。PBTZ169 和 H2-PBTZ169 在易感 H37Rv 和耐药 dprE1 突变菌株 NTB1 之间实现了 100% 的分离。这些发现支持了纳米运动技术在更快地检测针对 DprE1 酶的新型 MTB 候选药物的抗生素药敏性方面的潜力，该技术可缩短经验治疗时间，减少因治疗不准确而产生的抗生素耐药性选择压力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Antimicrobial Agents and Chemotherapy 医学-微生物学

CiteScore

10.00

自引率

8.20%

发文量

762

审稿时长

3 months

期刊介绍： Antimicrobial Agents and Chemotherapy (AAC) features interdisciplinary studies that build our understanding of the underlying mechanisms and therapeutic applications of antimicrobial and antiparasitic agents and chemotherapy.