000171664 001__ 171664
000171664 005__ 20260527123127.0
000171664 0247_ $$2doi$$a10.1186/s40249-026-01449-2
000171664 0248_ $$2sideral$$a149415
000171664 037__ $$aART-2026-149415
000171664 041__ $$aeng
000171664 100__ $$aCalvet-Seral, Juan
000171664 245__ $$aThe ribosomal RNA synthesis ratio biomarker in Mycobacterium ulcerans for drug activity evaluation
000171664 260__ $$c2026
000171664 5060_ $$aAccess copy available to the general public$$fUnrestricted
000171664 5203_ $$aBuruli 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).
000171664 536__ $$9info:eu-repo/grantAgreement/EC/H2020/853989/EU/EUROPEAN REGIMEN ACCELERATOR FOR TUBERCULOSIS/ERA4TB$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 853989-ERA4TB
000171664 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000171664 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000171664 700__ $$aSáez-López, Emma$$uUniversidad de Zaragoza
000171664 700__ $$aLópez-Expósito, Patricio R.
000171664 700__ $$aFerrer-Bazaga, Santiago
000171664 700__ $$aVaquero, Juan José
000171664 700__ $$0(orcid)0000-0002-8480-0325$$aRamón-García, Santiago
000171664 700__ $$aMendoza-Losana, Alfonso
000171664 7102_ $$11011$$2630$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Microbiología
000171664 773__ $$g15 (2026), 51 [11 pp.]$$pInfect. dis. poverty$$tInfectious diseases of poverty$$x2095-5162
000171664 8564_ $$s4924421$$uhttps://zaguan.unizar.es/record/171664/files/texto_completo.pdf$$yVersión publicada
000171664 8564_ $$s2507552$$uhttps://zaguan.unizar.es/record/171664/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000171664 909CO $$ooai:zaguan.unizar.es:171664$$particulos$$pdriver
000171664 951__ $$a2026-05-27-11:26:05
000171664 980__ $$aARTICLE