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Copy number variation (CNV) at specific genetic loci is associated with drug resistance and virulence, but information about its prevalence in endemic regions is limited. This study examines the drug resistance and virulence status of\n                      <jats:italic>Leishmania<\/jats:italic>\n                      strains in human and canine isolates from the Mediterranean region.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty-eight\n                      <jats:italic>Leishmania infantum<\/jats:italic>\n                      isolates were whole-genome sequenced with nanopore long reads, followed by de novo assembly. We analyzed chromosomal aneuploidies and gene copy number variation in loci linked to drug resistance and virulence in\n                      <jats:italic>Leishmania<\/jats:italic>\n                      , alongside the genomic structure and rearrangements responsible for these variations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Complete genomes were de novo assembled for 35\n                      <jats:italic>L. infantum<\/jats:italic>\n                      isolates (22 from dogs and 13 from humans), revealing significant chromosomal variability. We assessed copy number variation for 22 potential biomarkers: 15 genes related to drug resistance to first-line drugs (METK for allopurinol; LdSMT for amphotericin B; AQP1 and H-locus for antimonials; LdMT, LdRos3, and MSL for miltefosine; and PPM for paramomycin) and 7 genes related to virulence (lipophosphoglycan and proteophosphoglycan biosynthesis, and the Lack protein).\n                    <\/jats:p>\n                    <jats:p>Drug-resistance biomarkers were identified in 80% of the isolates. Canine strains primarily showed resistance to allopurinol and antimonials, while human isolates exhibited a broader resistance spectrum, especially to antimonials and paromomycin. The co-occurrence of resistance biomarkers was common, especially for allopurinol and antimonial resistance. Distinct mechanisms underlie the observed copy number variations. Virulence-associated genes were less variable among isolates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The prevalence of drug-resistance biomarkers in\n                      <jats:italic>Leishmania infantum<\/jats:italic>\n                      strains from the Mediterranean region, as revealed by this study, underscores the critical need for routine resistance surveillance in managing clinical leishmaniosis. These findings not only inform current clinical practice but also pave the way for more effective management strategies in the future.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-025-07105-2","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T07:44:54Z","timestamp":1764402294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area"],"prefix":"10.1186","volume":"19","author":[{"given":"Marina","family":"Carrasco-Martin","sequence":"first","affiliation":[]},{"given":"Joan","family":"Mart\u00ed-Carreras","sequence":"additional","affiliation":[]},{"given":"Marcel","family":"G\u00f3mez-Ponce","sequence":"additional","affiliation":[]},{"given":"Maria Magdalena","family":"Alcover","sequence":"additional","affiliation":[]},{"given":"Xavier","family":"Roura","sequence":"additional","affiliation":[]},{"given":"Llu\u00eds","family":"Ferrer","sequence":"additional","affiliation":[]},{"given":"Gad","family":"Baneth","sequence":"additional","affiliation":[]},{"given":"Federica","family":"Bruno","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Chicharro","sequence":"additional","affiliation":[]},{"given":"Anabela","family":"Cordeiro-da-Silva","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9","family":"Cristov\u00e3o","sequence":"additional","affiliation":[]},{"given":"Trentina","family":"Di Muccio","sequence":"additional","affiliation":[]},{"given":"Carla","family":"Maia","sequence":"additional","affiliation":[]},{"given":"Javier","family":"Moreno","sequence":"additional","affiliation":[]},{"given":"Anabel","family":"Priego","sequence":"additional","affiliation":[]},{"given":"Xavier","family":"Roca-Geron\u00e8s","sequence":"additional","affiliation":[]},{"given":"Nuno","family":"Santarem","sequence":"additional","affiliation":[]},{"given":"Anna Vila","family":"Soriano","sequence":"additional","affiliation":[]},{"given":"Fabrizio","family":"Vitale","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Yasur-Landau","sequence":"additional","affiliation":[]},{"given":"Olga","family":"Francino","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"7105_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006052","author":"A Ponte-Sucre","year":"2017","unstructured":"Ponte-Sucre A, Gamarro F, Dujardin JC, Barrett MP, L\u00f3pez-V\u00e9lez R, Garc\u00eda-Hern\u00e1ndez R, et al. 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