ArticleInfectious diseases of poverty2026
The ribosomal RNA synthesis ratio biomarker in Mycobacterium ulcerans for drug activity evaluation.
Article in Infectious diseases of poverty, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05169554 (Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy), which is not on this map. Not yet cited in PubMed.
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Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy: Comparison of 8 Weeks Standard Therapy (Rifampicin Plus Clarithromycin) vs. 4 Weeks Standard Plus Amoxicillin/Clavulanate Therapy [RC8 vs. RCA4]
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7 authors.
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Abstract
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).
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