Scholarlink

<p>Buruli ulcer (BU), a neglected tropical disease caused by <i>Mycobacterium ulcerans</i> (<i>Mul</i>), is treated with an 8-week regimen of rifampicin (RIF) and clarithromycin (CLA). Clinical trials are currently evaluating amoxicillin/clavulanate (AMX/CLV) co-administration to reduce treatment duration. However, conventional methods for assessing in vitro drug efficacy against <i>Mul</i>, like colony-forming units (CFUs), are slow and cumbersome. The ribosomal RNA synthesis ratio (RS-ratio) measures ribosome biogenesis and serves as a proxy of metabolic activity. While it is a promising predictive biomarker for treatment shortening in tuberculosis, its application in <i>Mul</i> remains unexplored. Here, we evaluated the RS-ratio for <i>Mul</i> drug activity assessment through RNA extractions from time-kill assays using RIF, CLA, and AMX/CLV, alone or in combinations. RIF + AMX/CLV-containing combinations produced a potent, rapid RS-ratio reduction, decreasing from a baseline of ≈2000 to ≈200 as early as day 3, and reaching their maximal inhibition (≈50–60) between days 7 and 10. Notably, this metabolic decline preceded the CFUs and luminescence drops observed in prior studies. Interestingly, the RS-ratio detected a metabolic recovery between days 14 and 28 (≈400), suggesting remaining bacterial viability, a phenomenon not observed by CFUs or luminescence. In summary, this is the first report using the RS-ratio to evaluate antibiotic activity against <i>Mul</i>. Our findings validate the RS-ratio as a molecular tool for assessing the sterilizing potential of new regimens to inform future research and clinical trial designs for the treatment of BU. Our results support the RIF + CLA + AMX/CLV regimen selection for BU treatment shortening in the BLMs4BU clinical trials (NCT05169554, PACTR202209521256638).</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The ribosomal RNA synthesis ratio biomarker in Mycobacterium ulcerans for drug activity evaluation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月8日

查看全文
  • Juan Calvet-Seral,
  • Emma Sáez-López,
  • Patricio R. López-Expósito,
  • Santiago Ferrer-Bazaga,
  • Juan José Vaquero,
  • Santiago Ramón-García,
  • Alfonso Mendoza-Losana

摘要

Buruli ulcer (BU), a neglected tropical disease caused by Mycobacterium ulcerans (Mul), is treated with an 8-week regimen of rifampicin (RIF) and clarithromycin (CLA). Clinical trials are currently evaluating amoxicillin/clavulanate (AMX/CLV) co-administration to reduce treatment duration. However, conventional methods for assessing in vitro drug efficacy against Mul, like colony-forming units (CFUs), are slow and cumbersome. The ribosomal RNA synthesis ratio (RS-ratio) measures ribosome biogenesis and serves as a proxy of metabolic activity. While it is a promising predictive biomarker for treatment shortening in tuberculosis, its application in Mul remains unexplored. Here, we evaluated the RS-ratio for Mul drug activity assessment through RNA extractions from time-kill assays using RIF, CLA, and AMX/CLV, alone or in combinations. RIF + AMX/CLV-containing combinations produced a potent, rapid RS-ratio reduction, decreasing from a baseline of ≈2000 to ≈200 as early as day 3, and reaching their maximal inhibition (≈50–60) between days 7 and 10. Notably, this metabolic decline preceded the CFUs and luminescence drops observed in prior studies. Interestingly, the RS-ratio detected a metabolic recovery between days 14 and 28 (≈400), suggesting remaining bacterial viability, a phenomenon not observed by CFUs or luminescence. In summary, this is the first report using the RS-ratio to evaluate antibiotic activity against Mul. Our findings validate the RS-ratio as a molecular tool for assessing the sterilizing potential of new regimens to inform future research and clinical trial designs for the treatment of BU. Our results support the RIF + CLA + AMX/CLV regimen selection for BU treatment shortening in the BLMs4BU clinical trials (NCT05169554, PACTR202209521256638).

Graphical Abstract