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Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis.

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dc.contributor.author Jara, Marlene
dc.contributor.author Arévalo Zelada, Jorge Luis
dc.contributor.author Llanos Cuentas, Elmer Alejandro
dc.contributor.author den Broeck, Frederik Van
dc.contributor.author Domagalska, Malgorzata Anna
dc.contributor.author Dujardin, Jean-Claude
dc.date.accessioned 2023-10-12T15:30:09Z
dc.date.available 2023-10-12T15:30:09Z
dc.date.issued 2023
dc.identifier.uri https://hdl.handle.net/20.500.12866/14298
dc.description.abstract INTRODUCTION: Resistance against anti-Leishmania drugs (DR) has been studied for years, giving important insights into long-term adaptations of these parasites to drugs, through genetic modifications. However, microorganisms can also survive lethal drug exposure by entering into temporary quiescence, a phenomenon called drug tolerance (DT), which is rather unexplored in Leishmania. METHODS: We studied a panel of nine Leishmania braziliensis strains highly susceptible to potassium antimonyl tartrate (PAT), exposed promastigotes to lethal PAT pressure, and compared several cellular and molecular parameters distinguishing DT from DR. RESULTS AND DISCUSSION: We demonstrated in vitro that a variable proportion of cells remained viable, showing all the criteria of DT and not of DR: i) signatures of quiescence, under drug pressure: reduced proliferation and significant decrease of rDNA transcription; ii) reversibility of the phenotype: return to low IC(50) after removal of drug pressure; and iii) absence of significant genetic differences between exposed and unexposed lineages of each strain and absence of reported markers of DR. We found different levels of quiescence and DT among the different L. braziliensis strains. We provide here a new in-vitro model of drug-induced quiescence and DT in Leishmania. Research should be extended in vivo, but the current model could be further exploited to support R&D, for instance, to guide the screening of compounds to overcome the quiescence resilience of the parasite, thereby improving the therapy of leishmaniasis. en_US
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartofseries Frontiers in Cellular and Infection Microbiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Leishmania en_US
dc.subject Antimonials en_US
dc.subject Quiescence en_US
dc.subject Drug tolerance en_US
dc.subject Persisters en_US
dc.subject.mesh Leishmania
dc.subject.mesh Antimonio
dc.subject.mesh Tolerancia a Medicamentos
dc.title Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis. en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3389/fcimb.2023.1253033
dc.relation.issn 2235-2988


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