01677nas a2200241   4500000000100000008004100001260001200042653001900054653002000073653001500093100001800108700001600126700001000142700001400152700001700166700001300183245008000196856007500276300001000351490000700361520105300368022001401421       2026                            d  c06/202610adrug responses10aDrug Resistance10aLeishmania1 ade Oliveira B1 aDel Angel J1 aMay N1 aBarrett M1 aDomagalska M1 aBeneke T00aBeyond resistance: Emerging methods to dissect drug responses in Leishmania  uhttps://pmc.ncbi.nlm.nih.gov/articles/PMC13293385/pdf/ppat.1014331.pdf  a1 - 70 v223 a<p>Treatment failure and relapse remain major challenges in leishmaniasis despite available chemotherapies. Historically, these outcomes have been interpreted through the lens of classical drug resistance driven by heritable genetic mutations. However, drug responses are increasingly recognised to extend beyond resistance and include distinct but related phenomena such as hypersensitivity, tolerance, and persistence. Dissecting this range of responses in Leishmania requires approaches that capture both heritable genetic variation and dynamic cellular states. Here, we highlight how emerging genomics and perturb-omics technologies can resolve mechanisms underlying diverse drug responses. We emphasise that their impact depends on state-aware experimental design, including calibrated drug-selection, varied exposure regimens, and strategies to isolate rare persister populations. Together, these approaches provide a framework to move beyond resistance-centric models towards a more comprehensive understanding of parasite drug response.</p>  a1553-7374