Publicação
Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area
| Resumo: | BACKGROUND: Drug-resistant strains of Leishmania infantum challenge the effectiveness of treatments for clinical leishmaniosis and may lead to more frequent relapses. 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 Leishmania strains in human and canine isolates from the Mediterranean region. METHODS: Forty-eight Leishmania infantum 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 Leishmania, alongside the genomic structure and rearrangements responsible for these variations. RESULTS: Complete genomes were de novo assembled for 35 L. infantum 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). 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. CONCLUSIONS: The prevalence of drug-resistance biomarkers in Leishmania infantum 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. |
|---|---|
| Autores principais: | Carrasco-Martin, Marina |
| Outros Autores: | Martí-Carreras, Joan; Gómez-Ponce, Marcel; Alcover, Maria Magdalena; Roura, Xavier; Ferrer, Lluís; Baneth, Gad; Bruno, Federica; Chicharro, Carmen; Cordeiro da Silva, Anabela; Cristovão, José; Di Muccio, Trentina; Maia, Carla; Moreno, Javier; Priego, Anabel; Roca-Geronès, Xavier; Santarem, Nuno; Soriano, Anna Vila; Vitale, Fabrizio; Yasur-Landau, Daniel; Francino, Olga |
| Assunto: | Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| Ano: | 2026 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| _version_ | 1869289198837563392 |
|---|---|
| author | Carrasco-Martin, Marina |
| author2 | Martí-Carreras, Joan Gómez-Ponce, Marcel Alcover, Maria Magdalena Roura, Xavier Ferrer, Lluís Baneth, Gad Bruno, Federica Chicharro, Carmen Cordeiro da Silva, Anabela Cristovão, José Di Muccio, Trentina Maia, Carla Moreno, Javier Priego, Anabel Roca-Geronès, Xavier Santarem, Nuno Soriano, Anna Vila Vitale, Fabrizio Yasur-Landau, Daniel Francino, Olga |
| author2_role | author author author author author author author author author author author author author author author author author author author author |
| author_facet | Carrasco-Martin, Marina Martí-Carreras, Joan Gómez-Ponce, Marcel Alcover, Maria Magdalena Roura, Xavier Ferrer, Lluís Baneth, Gad Bruno, Federica Chicharro, Carmen Cordeiro da Silva, Anabela Cristovão, José Di Muccio, Trentina Maia, Carla Moreno, Javier Priego, Anabel Roca-Geronès, Xavier Santarem, Nuno Soriano, Anna Vila Vitale, Fabrizio Yasur-Landau, Daniel Francino, Olga |
| author_role | author |
| contributor_name_str_mv | Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo FCT) Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT) Vector borne diseases and pathogens (VBD) BioMed Central (BMC) RUN |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Carrasco-Martin, Marina\"},{\"Person.name\":\"Martí-Carreras, Joan\"},{\"Person.name\":\"Gómez-Ponce, Marcel\"},{\"Person.name\":\"Alcover, Maria Magdalena\"},{\"Person.name\":\"Roura, Xavier\"},{\"Person.name\":\"Ferrer, Lluís\"},{\"Person.name\":\"Baneth, Gad\"},{\"Person.name\":\"Bruno, Federica\"},{\"Person.name\":\"Chicharro, Carmen\"},{\"Person.name\":\"Cordeiro da Silva, Anabela\"},{\"Person.name\":\"Cristovão, José\"},{\"Person.name\":\"Di Muccio, Trentina\"},{\"Person.name\":\"Maia, Carla\"},{\"Person.name\":\"Moreno, Javier\"},{\"Person.name\":\"Priego, Anabel\"},{\"Person.name\":\"Roca-Geronès, Xavier\"},{\"Person.name\":\"Santarem, Nuno\"},{\"Person.name\":\"Soriano, Anna Vila\"},{\"Person.name\":\"Vitale, Fabrizio\"},{\"Person.name\":\"Yasur-Landau, Daniel\"},{\"Person.name\":\"Francino, Olga\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo FCT) Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT) Vector borne diseases and pathogens (VBD) BioMed Central (BMC) RUN |
| datacite.creators.creator.creatorName.fl_str_mv | Carrasco-Martin, Marina Martí-Carreras, Joan Gómez-Ponce, Marcel Alcover, Maria Magdalena Roura, Xavier Ferrer, Lluís Baneth, Gad Bruno, Federica Chicharro, Carmen Cordeiro da Silva, Anabela Cristovão, José Di Muccio, Trentina Maia, Carla Moreno, Javier Priego, Anabel Roca-Geronès, Xavier Santarem, Nuno Soriano, Anna Vila Vitale, Fabrizio Yasur-Landau, Daniel Francino, Olga |
| datacite.date.Accepted.fl_str_mv | 2026-12-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2026-06-26T16:28:03Z |
| datacite.date.embargoed.fl_str_mv | 2026-06-26T16:28:03Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| datacite.titles.title.fl_str_mv | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| dc.contributor.none.fl_str_mv | Instituto de Higiene e Medicina Tropical (IHMT) Global Health and Tropical Medicine (GHTM) Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo FCT) Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT) Vector borne diseases and pathogens (VBD) BioMed Central (BMC) RUN |
| dc.creator.none.fl_str_mv | Carrasco-Martin, Marina Martí-Carreras, Joan Gómez-Ponce, Marcel Alcover, Maria Magdalena Roura, Xavier Ferrer, Lluís Baneth, Gad Bruno, Federica Chicharro, Carmen Cordeiro da Silva, Anabela Cristovão, José Di Muccio, Trentina Maia, Carla Moreno, Javier Priego, Anabel Roca-Geronès, Xavier Santarem, Nuno Soriano, Anna Vila Vitale, Fabrizio Yasur-Landau, Daniel Francino, Olga |
| dc.date.Accepted.fl_str_mv | 2026-12-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2026-06-26T16:28:03Z |
| dc.date.embargoed.fl_str_mv | 2026-06-26T16:28:03Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10362/204136 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| dc.title.fl_str_mv | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | BACKGROUND: Drug-resistant strains of Leishmania infantum challenge the effectiveness of treatments for clinical leishmaniosis and may lead to more frequent relapses. 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 Leishmania strains in human and canine isolates from the Mediterranean region. METHODS: Forty-eight Leishmania infantum 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 Leishmania, alongside the genomic structure and rearrangements responsible for these variations. RESULTS: Complete genomes were de novo assembled for 35 L. infantum 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). 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. CONCLUSIONS: The prevalence of drug-resistance biomarkers in Leishmania infantum 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://run.unl.pt/bitstreams/9537c59f-c90a-4901-a932-b2605d40a3ac/download |
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| identifier.url.fl_str_mv | http://hdl.handle.net/10362/204136 |
| inst_facet_str | urn:organizationAcronym:unl{{{_:::_}}}Universidade Nova de Lisboa |
| instacron_str | unl |
| institution | Universidade Nova de Lisboa |
| instname_str | Universidade Nova de Lisboa |
| language | eng |
| network_acronym_str | run |
| network_name_str | Repositório Institucional da UNL |
| oai_identifier_str | oai:run.unl.pt:10362/204136 |
| organization_str_mv | urn:organizationAcronym:unl |
| person_str_mv | Carrasco-Martin, Marina Martí-Carreras, Joan Gómez-Ponce, Marcel Alcover, Maria Magdalena Roura, Xavier Ferrer, Lluís Baneth, Gad Bruno, Federica Chicharro, Carmen Cordeiro da Silva, Anabela Cristovão, José Di Muccio, Trentina Maia, Carla Moreno, Javier Priego, Anabel Roca-Geronès, Xavier Santarem, Nuno Soriano, Anna Vila Vitale, Fabrizio Yasur-Landau, Daniel Francino, Olga |
| publishDate | 2026 |
| repo_facet_str | urn:repositoryAcronym:run{{{_:::_}}}Repositório Institucional da UNL |
| reponame_str | Repositório Institucional da UNL |
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| spelling | engenBACKGROUND: Drug-resistant strains of Leishmania infantum challenge the effectiveness of treatments for clinical leishmaniosis and may lead to more frequent relapses. 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 Leishmania strains in human and canine isolates from the Mediterranean region. METHODS: Forty-eight Leishmania infantum 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 Leishmania, alongside the genomic structure and rearrangements responsible for these variations. RESULTS: Complete genomes were de novo assembled for 35 L. infantum 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). 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. CONCLUSIONS: The prevalence of drug-resistance biomarkers in Leishmania infantum 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.application/pdfenInsights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean areaCarrasco-Martin, MarinaMartí-Carreras, JoanGómez-Ponce, MarcelAlcover, Maria MagdalenaRoura, XavierFerrer, LluísBaneth, GadBruno, FedericaChicharro, CarmenCordeiro da Silva, AnabelaCristovão, JoséDi Muccio, TrentinaMaia, CarlaMoreno, JavierPriego, AnabelRoca-Geronès, XavierSantarem, NunoSoriano, Anna VilaVitale, FabrizioYasur-Landau, DanielFrancino, OlgaInstituto de Higiene e Medicina Tropical (IHMT)Global Health and Tropical Medicine (GHTM)Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo FCT)Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo IHMT)Vector borne diseases and pathogens (VBD)BioMed Central (BMC)HostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf1756-3305URNIsPartOfPURE: 160090831URNIsPartOfPURE UUID: 27a88d8b-79fc-46af-8964-6c9f71976afeURNIsPartOfPubMed: 41318579URNIsPartOfPubMedCentral: PMC12802309URNIsPartOfScopus: 105027469057URNIsPartOfWOS: 001661242100001URNIsPartOfORCID: /0000-0002-2545-7686/work/212614233DOIIsPartOf10.1186/s13071-025-07105-22026-06-26T16:28:03Z2026-122026-12-01T00:00:00ZHandlehttp://hdl.handle.net/10362/204136http://purl.org/coar/access_right/c_abf2open accessLeishmania infantum/geneticsDogsHumansAnimalsVirulence/geneticsAntiprotozoal Agents/pharmacologyDrug Resistance/geneticsDNA Copy Number VariationsLeishmaniasis, Visceral/parasitologyMediterranean Region/epidemiologyGenome, ProtozoanDog Diseases/parasitologyWhole Genome SequencingCohort Studies3129706 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/9537c59f-c90a-4901-a932-b2605d40a3ac/download |
| spellingShingle | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area Carrasco-Martin, Marina Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| status | SINGLETON |
| subject.fl_str_mv | Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| title | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| title_full | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| title_fullStr | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| title_full_unstemmed | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| title_short | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| title_sort | Insights on genomic profiles of drug resistance and virulence in a cohort of Leishmania infantum isolates from the Mediterranean area |
| topic | Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| topic_facet | Leishmania infantum/genetics Dogs Humans Animals Virulence/genetics Antiprotozoal Agents/pharmacology Drug Resistance/genetics DNA Copy Number Variations Leishmaniasis, Visceral/parasitology Mediterranean Region/epidemiology Genome, Protozoan Dog Diseases/parasitology Whole Genome Sequencing Cohort Studies |
| url | http://hdl.handle.net/10362/204136 |
| visible | 1 |