Active transcriptome remodeling underlies antimony-induced drug tolerance in persister-like Leishmania parasites.

Active transcriptome remodeling enables Leishmania mexicana persister-like parasites to survive antimony treatment, with 316 genes downregulated and 241 upregulated during drug tolerance.

• Why it matters: Understanding the molecular basis of persistence is crucial because it underpins treatment failure and relapse in leishmaniasis, yet the mechanisms remain poorly characterized in these parasites.
• What they did: The study developed a model using Ficoll density gradient centrifugation after potassium antimonyl tartrate exposure, followed by transcriptomic profiling across stress, recovery, and rechallenge phases to identify gene expression changes.
• The result: Findings reveal that persistence involves active transcriptome reprogramming, including epigenetic and epitranscriptomic modifications, which transiently resemble resistance and offer potential targets to prevent relapse.