Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis
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...
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2023
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| author | Marlene Jara Jorge Arévalo Alejandro Llanos‐Cuentas Frederik Van den Broeck Malgorzata A. Domagalska Jean‐Claude Dujardin |
| author_browse | Alejandro Llanos‐Cuentas Frederik Van den Broeck Jean‐Claude Dujardin Jorge Arévalo Malgorzata A. Domagalska Marlene Jara |
| author_facet | Marlene Jara Jorge Arévalo Alejandro Llanos‐Cuentas Frederik Van den Broeck Malgorzata A. Domagalska Jean‐Claude Dujardin |
| author_sort | Marlene Jara |
| collection | Producción científica |
| description | 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. |
| format | Article |
| id | oai:cris.upeu.edu.pe:20.500.15037/901 |
| institution | UPeU |
| language | English |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
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| spelling | oai:cris.upeu.edu.pe:20.500.15037/9012026-10-30T16:14:58ZUnveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasisMarlene JaraJorge ArévaloAlejandro Llanos‐CuentasFrederik Van den BroeckMalgorzata A. DomagalskaJean‐Claude DujardinLeishmaniaLeishmania braziliensisBiologyDrugDrug resistanceCutaneous leishmaniasisMicrobiologyIn vitroLeishmaniasisLeishmania majorPhenotypeIn vivoParasite hostingImmunologyGeneticsPharmacologyGeneWorld Wide WebComputer scienceLeishmaniaLeishmania braziliensisBiologyDrugDrug resistanceCutaneous leishmaniasisMicrobiologyIn vitroLeishmaniasisLeishmania majorPhenotypeIn vivoParasite hostingImmunologyGeneticsPharmacologyGeneHumansHumansHumansLeishmaniaLeishmaniaLeishmaniaLeishmania braziliensis geneticsLeishmania braziliensis geneticsLeishmania braziliensis geneticsLeishmaniasis, Cutaneous drug therapyLeishmaniasis, Cutaneous drug therapyLeishmaniasis, Cutaneous drug therapyLeishmaniasis, Cutaneous parasitologyLeishmaniasis, Cutaneous parasitologyLeishmaniasis, Cutaneous parasitologyHealth Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis StudiesHealth Sciences Medicine Epidemiology Trypanosoma species research and implicationsLife Sciences Agricultural and Biological Sciences Insect Science Insect and Pesticide ResearchIntroduction 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.Articlehttps://pubmed.ncbi.nlm.nih.gov/37790908https://www.frontiersin.org/articles/10.3389/fcimb.2023.1253033/pdf?isPublishedV2=Falsehttps://doi.org/10.3389/fcimb.2023.125303310.3389/fcimb.2023.1253033https://hdl.handle.net/20.500.15037/901W4386850529enFrontiers in Cellular and Infection Microbiology2235-29882023-09-182026-06-13T09:39:59Z2026-06-13T09:39:59Z |
| spellingShingle | Leishmania Leishmania braziliensis Biology Drug Drug resistance Cutaneous leishmaniasis Microbiology In vitro Leishmaniasis Leishmania major Phenotype In vivo Parasite hosting Immunology Genetics Pharmacology Gene World Wide Web Computer science Leishmania Leishmania braziliensis Biology Drug Drug resistance Cutaneous leishmaniasis Microbiology In vitro Leishmaniasis Leishmania major Phenotype In vivo Parasite hosting Immunology Genetics Pharmacology Gene Humans Humans Humans Leishmania Leishmania Leishmania Leishmania braziliensis genetics Leishmania braziliensis genetics Leishmania braziliensis genetics Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Health Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis Studies Health Sciences Medicine Epidemiology Trypanosoma species research and implications Life Sciences Agricultural and Biological Sciences Insect Science Insect and Pesticide Research Marlene Jara Jorge Arévalo Alejandro Llanos‐Cuentas Frederik Van den Broeck Malgorzata A. Domagalska Jean‐Claude Dujardin Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| title | Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| title_full | Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| title_fullStr | Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| title_full_unstemmed | Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| title_short | Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| title_sort | unveiling drug tolerant and persister like cells in leishmania braziliensis lines derived from patients with cutaneous leishmaniasis |
| topic | Leishmania Leishmania braziliensis Biology Drug Drug resistance Cutaneous leishmaniasis Microbiology In vitro Leishmaniasis Leishmania major Phenotype In vivo Parasite hosting Immunology Genetics Pharmacology Gene World Wide Web Computer science Leishmania Leishmania braziliensis Biology Drug Drug resistance Cutaneous leishmaniasis Microbiology In vitro Leishmaniasis Leishmania major Phenotype In vivo Parasite hosting Immunology Genetics Pharmacology Gene Humans Humans Humans Leishmania Leishmania Leishmania Leishmania braziliensis genetics Leishmania braziliensis genetics Leishmania braziliensis genetics Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Health Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis Studies Health Sciences Medicine Epidemiology Trypanosoma species research and implications Life Sciences Agricultural and Biological Sciences Insect Science Insect and Pesticide Research |
| topic_facet | Leishmania Leishmania braziliensis Biology Drug Drug resistance Cutaneous leishmaniasis Microbiology In vitro Leishmaniasis Leishmania major Phenotype In vivo Parasite hosting Immunology Genetics Pharmacology Gene World Wide Web Computer science Leishmania Leishmania braziliensis Biology Drug Drug resistance Cutaneous leishmaniasis Microbiology In vitro Leishmaniasis Leishmania major Phenotype In vivo Parasite hosting Immunology Genetics Pharmacology Gene Humans Humans Humans Leishmania Leishmania Leishmania Leishmania braziliensis genetics Leishmania braziliensis genetics Leishmania braziliensis genetics Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous drug therapy Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Leishmaniasis, Cutaneous parasitology Health Sciences Medicine Public Health, Environmental and Occupational Health Research on Leishmaniasis Studies Health Sciences Medicine Epidemiology Trypanosoma species research and implications Life Sciences Agricultural and Biological Sciences Insect Science Insect and Pesticide Research |
| url | https://pubmed.ncbi.nlm.nih.gov/37790908 https://www.frontiersin.org/articles/10.3389/fcimb.2023.1253033/pdf?isPublishedV2=False https://doi.org/10.3389/fcimb.2023.1253033 https://hdl.handle.net/20.500.15037/901 |
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