{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:03:13Z","timestamp":1791266593859,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Resistance against anti-\n                      <jats:italic>Leishmania<\/jats:italic>\n                      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\n                      <jats:italic>Leishmania<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied a panel of nine\n                      <jats:italic>Leishmania braziliensis<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      We demonstrated\n                      <jats:italic>in vitro<\/jats:italic>\n                      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\n                      <jats:sub>50<\/jats:sub>\n                      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\n                      <jats:italic>L. braziliensis<\/jats:italic>\n                      strains. We provide here a new\n                      <jats:italic>in-vitro<\/jats:italic>\n                      model of drug-induced quiescence and DT in\n                      <jats:italic>Leishmania<\/jats:italic>\n                      . Research should be extended\n                      <jats:italic>in vivo<\/jats:italic>\n                      , but the current model could be further exploited to support R&amp;amp;D, for instance, to guide the screening of compounds to overcome the quiescence resilience of the parasite, thereby improving the therapy of leishmaniasis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2023.1253033","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T02:25:57Z","timestamp":1695090357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Unveiling drug-tolerant and persister-like cells in Leishmania braziliensis lines derived from patients with cutaneous leishmaniasis"],"prefix":"10.3389","volume":"13","author":[{"given":"Marlene","family":"Jara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Arevalo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Llanos-Cuentas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik Van den","family":"Broeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata Anna","family":"Domagalska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Dujardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02095-17","article-title":"Complex interplay between sphingolipid and sterol metabolism revealed by perturbations to the leishmania metabolome caused by miltefosine","volume":"62","author":"Armitage","year":"2018","journal-title":"Antimicrob. 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