Caracterización de la respuesta de Leishmania (Viannia) guyanensis a fármacos de utilidad clínica en el tratamiento de leishmaniasis cutánea mediante herramientas de genómica funcional

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dc.contributor.advisorClavijo Ramírez, Carlos Arturospa
dc.contributor.advisorUrrea Montes, Daniel Alfonsospa
dc.contributor.authorBonilla Valbuena, Liliana Alejandraspa
dc.date.accessioned2025-11-28T20:16:46Z
dc.date.available2025-11-28T20:16:46Z
dc.date.issued2025-09
dc.descriptionilustraciones, gráficas, mapas, tablasspa
dc.description.abstractLa leishmaniasis cutánea (LC) es la forma clínica más frecuente de leishmaniasis tegumentaria y constituye un importante problema de salud pública en Colombia. El antimoniato de meglumina (Glucantime®) es la primera opción terapéutica y como segunda línea de tratamiento se emplean la miltefosina y la anfotericina B, siendo esta última utilizada en casos de falla terapéutica o contraindicación para la terapia con derivados del antimonio (Sbv). El presente estudio caracterizó la respuesta de Leishmania (Viannia) guyanensis a fármacos de utilidad clínica en el tratamiento de leishmaniasis cutánea mediante herramientas de genómica estructural y funcional. Se determinaron los perfiles de susceptibilidad a Glucantime® en el estadio amastigote de dos aislados clínicos de L. (V.) guyanensis provenientes de pacientes con LC. Además, se analizaron sus genomas completos para identificar variaciones estructurales (ploidía y variación en el número de copias génicas), con el fin de seleccionar genes candidatos posiblemente asociados a mecanismos de tolerancia a Glucantime®. También se evaluó la susceptibilidad in vitro en promastigotes de líneas knockout de L. (V.) braziliensis con deleciones en los genes que codifican la Latosterol Oxidasa (LO) y la proteína de membrana asociada a vesículas (Vamp), previamente asociados con mecanismos de tolerancia a anfotericina B y miltefosina. Los resultados muestran que existen diferencias estructurales genómicas entre aislados clínicos de L. (V.) guyanensis con diferentes niveles de susceptibilidad a Glucantime®. El análisis de CNVs mostró que el aislado más tolerante presenta variación en número de copias génicas, en genes asociados a tolerancia a Glucantime® (transportador de pteridina, HSP70, transportador ABC), infección y proliferación intracelular (GP63, Amastinas, MIPS, Fosfatasas de proteína serina/treonina). Las líneas knockout de L. (V.) braziliensis en los genes LO y Vamp mostraron una mayor tolerancia in vitro, a los fármacos evaluados en comparación con la cepa de referencia. Lo anterior sugiere posibles relaciones entre las variaciones estructurales genómicas y el fenotipo de tolerancia observado in vitro, lo cual brinda una ruta para elucidar los mecanismos moleculares asociados con la disminución en la susceptibilidad a fármacos de uso clínico en Leishmania. (Texto tomado de la fuente).spa
dc.description.abstractCutaneous leishmaniasis (CL) is the most common clinical form of leishmaniasis and constitutes a major public health problem in Colombia. Meglumine antimony (glucantime®) is the first-line treatment, and as a second line of treatment, miltefosine and amphotericin B are used, the latter being used in cases of therapeutic failure or contraindication for antimony derivatives (Sbv). The present study characterized the response of Leishmania (Viannia) guyanensis to clinically relevant drugs used in the treatment of cutaneous leishmaniasis through structural and functional genomics tools. The susceptibility profiles to Glucantime® were determined in the amastigote stage of two clinical isolates of L. (V.) guyanensis obtained from patients with CL. Additionally, whole-genome analysis was performed to identify structural variations (ploidy and CNVs), with the aim of selecting candidate genes potentially associated with Glucantime® tolerance mechanisms. In addition, in vitro susceptibility was evaluated in promastigotes of L. (V.) braziliensis knockout lines with deletions in the genes encoding Lanosterol Oxidase (LO) and Vesicle-Associated Membrane Protein (Vamp), previously associated with tolerance mechanisms to amphotericin B and miltefosine. The results show that there are structural genomic differences between clinical isolates of L. (V.) guyanensis with distinct levels of susceptibility to Glucantime®. The CNV analysis showed that the most tolerant isolate presents copy number variation, in genes associated with Glucantime® tolerance (pteridine transporter, HSP70, ABC transporter), infection and intracellular proliferation (GP63, amastins, MIPS, serine/threonine protein phosphatases). The knockout lines of L. (V.) braziliensis in the LO and Vamp genes showed greater tolerance in vitro to the evaluated drugs compared to the reference strain. These findings suggest possible relationship between structural genomic variations and the observed tolerance phenotype in vitro, which could bring about a way to elucidate the molecular mechanisms associated with reduced susceptibility to clinically used drugs in Leishmania.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Biologíaspa
dc.description.notesAnexo 1. Marcación de Macrófagos Infectados con Leishmania guyanensis con Hoechst 33342 y Fijados con PFA. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1d6bLjZZQcFdR5BrA7wPnpatSSO13CSG7/view?usp=drive_link Anexo 2. Evaluación del efecto de gelatina como matriz extracelular, en la diferenciación de células U937 inducida por PMA. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1PYnYz7cK5nlrpn9J45B0B_hHXO3Sizp/view?usp=drive_link Anexo 3. Determinación de la proporción de parásitos de Leishmania guyanensis por monocito U937 sembrado en macrófagos. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1tqJJ9UnyMhuaF7fzixdXAFpJULJk0GfQ/view?usp=drive_link Anexo 4. Determinación visual del porcentaje de infección de macrófagos infectados. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1x5QN7fxVFiWVBL0WKxCx0TRbMPSCXo6K/view?usp=drive_lin k Anexo 5. Determinación de los perfiles de susceptibilidad in vitro de aislamientos clínicos de Leishmania (V.) guyanensis. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1VfIiq8EPFyZzUkLi-cr9k0qf1lgoldUU/view?usp=drive_link Anexo 6. Valores de calidad Phred de lecturas Illumina pareadas. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1kjjso4Och6K0CTWMwnirOWfqca24cFrZ/view?usp=drive_link Anexo 7. Anotación genómica de L. (V.) guyanensis M4147 mediante el servidor web Companion. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1NK7_vZr2jiUuu06sFCnZhZSDeFc4qHTW/view?usp=drive_link Anexo 8. Mapa del plásmido pTB007_Cas9_T7_Viannia. 133 El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/19oW-AuJLVVrcxREpnFrASwI9GAYd9YY/view?usp=drive_link Anexo 9. Determinación de la concentración de Higromicina B. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1vLldJFdVzvPzrg4L3zF2LOP1wkjnSyti/view?usp=drive_link Anexo 10. Validación de la transfección y expresión del plásmido pTB007_Viannia. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1WZ7Jufb0GjETCgzkAVIwYpSEKVN0gzvn/view?usp=drive_link Anexo 11. Validación del reemplazo del primer alelo de los genes LO y Vamp mediante PCR diagnóstica. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1mA3wTYjH0AM6lqTSG9j-g4js9GQYiGQ/view?usp=drive_link Anexo 12. IC50 en promastigotes modificados genéticamente de L. (V.) braziliensis. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/18GKZQ9- 1BBpbejU2PagcMeCI7QEIP_uL/view?usp=drive_link Anexo 13. Comparaciones múltiples post-hoc (Dunn o Tukey) para analizar las diferencias entre concentraciones en cada cepa. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1guNWr6rU5akUJCoXDxbkwU2kaRrqFpAZ/view?usp=drive_link Anexo 14. Distribución de profundidad de los cromosomas en L. guyanensis. El protocolo está disponible en el siguiente enlace: https://drive.google.com/file/d/1Yfq7v4YijfcJGgaA5E4k1cZtmYNJF6cU/view?usp=drive_link Anexo 15. Comparaciones pareadas de CNVs entre las cuatro cepas mediante el estadístico z-score. El protocolo está disponible en el siguiente enlace: https://docs.google.com/spreadsheets/d/19QH2UNXU_DaXzo6GjK02EZw4eRguVPr/edit?usp=drive_link&ouid=115883201584941521069&rtpof=true&sd=true Anexo 16. CNVs y Proteínas Hipotéticas. El protocolo está disponible en el siguiente enlace: https://docs.google.com/spreadsheets/d/16CRovWse8DBWbML469jXFV0rSLxhb7KN/edit?usp= drive_link&ouid=115883201584941521069&rtpof=true&sd=truespa
dc.description.sponsorshipEsta investigación fue financiada gracias al apoyo económico otorgado a través de la Convocatoria para el desarrollo de tesis de posgrado (Maestría de Investigación y Doctorado) del programa de Biología, Facultad de Ciencias, Sede Bogotá de la Universidad Nacional de Colombia 2024. Adicionalmente, se contó con el apoyo de la Convocatoria para el desarrollo de tesis de posgrado (Maestría de Investigación y Doctorado) de la Facultad de Ciencias Sede Bogotá de la Universidad Nacional de Colombia 2024 (Proyecto HERMES 62258).spa
dc.format.extent133 páginasspa
dc.format.mimetypeapplication/pdf
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/89162
dc.language.isospa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Biologíaspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Biologíaspa
dc.relation.indexedBiremespa
dc.relation.referencesAbadías-Granado, I., Diago, A., Cerro, P. A., Palma-Ruiz, A. M., & Gilaberte, Y. (2021). Leishmaniasis cutánea y mucocutánea. Actas Dermo-Sifiliográficas, 112(7), 601-618. https://doi.org/10.1016/j.ad.2021.02.008
dc.relation.referencesAdaui, V., Kröber-Boncardo, C., Brinker, C., Zirpel, H., Sellau, J., Arévalo, J., Dujardin, J. C., & Clos, J. (2020). Application of CRISPR/Cas9-Based Reverse Genetics in Leishmania braziliensis: Conserved Roles for HSP100 and HSP23. Genes (Basel), 11(10), 1159. doi: 10.3390/genes11101159.
dc.relation.referencesAlcolea, P. J., Alonso, A., Degayón, M. A., Moreno-Paz, M., Jiménez, M., Molina, R., Gómez, M. J., & Larraga, V. (2016). In vitro infectivity and differential gene expression of Leishmania infantum metacyclic promastigotes: Negative selection with peanut agglutinin in culture versus isolation from the stomodeal valve of Phlebotomus perniciosus. BMC Genomics, 17(1), 1-14. https://doi.org/10.1186/s12864-016-2672-8
dc.relation.referencesAlpizar-Sosa, E. A., Zimbres, F. M., Mantilla, B. S., Dickie, E. A., Wei, W., Burle-Caldas, G. A., ... Denny, P. W. (2024). Evaluation of the Leishmania inositol phosphorylceramide synthase as a drug target using a chemical and genetic approach. ACS Infectious Diseases, 10(8), 2913–2928. https://doi.org/10.1021/acsinfecdis.4c00284
dc.relation.referencesAlves, M. J. M., & Colli, W. (2008). Role of the gp85/trans‐sialidase superfamily of glycoproteins in the interaction of Trypanosoma cruzi with host structures. In Subcellular Biochemistry (Vol. 47, pp. 58–69). https://doi.org/10.1007/978-0-387-78267-6_4
dc.relation.referencesAmorim, C. F., Novais, F. O., Nguyen, B. T., Misic, A. M., Carvalho, L. P., Carvalho, E. M., & Scott, P. (2019). Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis. Science Translational Medicine, 11(519), eaax4204. doi:10.1126/scitranslmed.aax4204.
dc.relation.referencesAndrews, S. (2010). FastQC: A quality control tool for high throughput sequence data 109 [Software]. Babraham Bioinformatics. http://www.bioinformatics.babraham.ac.uk/projects/fastqc
dc.relation.referencesBahrami, A., Mohebali, M., Nafchi, H. R., Raoofian, R., Kazemirad, E., & Hajjaran, H. (2022). Overexpression of iron super oxide dismutases A/B genes are associated with antimony resistance of Leishmania tropica clinical isolates. Iranian Journal of Parasitology, 17(4), 473–482.
dc.relation.referencesBates, P. A. (2018). Revising Leishmania´s life cycle. Nature Microbiology, 3(5), 529-530. doi:10.1038/s41564-018-0154-2.
dc.relation.referencesBatra, D., Lin, W., Narayanan, V., Rowe, L. A., Sheth, M., Zheng, Y., Loparev, V., & de Almeida, M. (2019). Draft genome sequences of Leishmania (Leishmania) amazonensis, Leishmania (Leishmania) mexicana, and Leishmania (Leishmania) aethiopica, potential etiological agents of diffuse cutaneous leishmaniasis. Microbiology Resource Announcements, 8, e00269-19. https://doi.org/10.1128/mra.00269-19
dc.relation.referencesBendtsen, J.D., Jensen, L.J., Blom, N., Von Heijne, G., & Brunak, S. (2004). Feature-based prediction of non-classical and leaderless protein secretion. Protein Eng Des Sel, 17: 349-356.
dc.relation.referencesBeneke, T., & Gluenz, E. (2019). LeishGEdit: A Method for Rapid Gene Knockout and Tagging Using CRISPR-Cas9. Methods in Molecular Biology, 1971, 189–210. doi: 10.1007/978-1-4939-9210-2_9.
dc.relation.referencesBeneke, T., Madden, R., Makin, L., Valli, J., Sunter, J., & Gluenz, E. (2017). A CRISPR Cas9 high-throughput genome editing toolkit for kinetoplastids. Royal Society Open Science, 4(5), 170095. https://doi.org/10.1098/rsos.170095
dc.relation.referencesBhandari, V., Kulshrestha, A., Deep, D. K., Stark, O., Prajapati, V. K., Ramesh, V., Sundar, S., Schonian, G., Dujardin, J. C., & Salotra, P. (2012). Drug susceptibility in Leishmania isolates following miltefosine treatment in cases of visceral leishmaniasis and post kala-azar dermal leishmaniasis. PLoS Neglected Tropical Diseases, 6(5), e1657. https://doi.org/10.1371/journal.pntd.0001657
dc.relation.referencesBhandari, V., Sundar, S., Dujardin, J. C., & Salotra, P. (2014). Elucidation of cellular mechanisms involved experimental paromomycin resistance in Leishmania 110 donovani. Antimicrobial Agents and Chemotherapy, 58(5), 2580-2585. https://doi.org/10.1128/AAC.01574-13
dc.relation.referencesBharadava, K., Upadhyay, T. K., Kaushal, R. S., Ahmad, I., Alraey, Y., Siddiqui, S., & Saeed, M. (2024). Genomic insight of Leishmania parasite: In-depth review of drug resistance mechanisms and genetic mutations. ACS Omega, 9(11), 12500-12514. https://doi.org/10.1021/acsomega.3c09400
dc.relation.referencesBogdan, C., & Röllinghoff, M. (1998). The immune response to Leishmania: Mechanisms of parasite control and evasion. International Journal for Parasitology, 28(1), 121–134. https://doi.org/10.1016/S0020-7519(97)00169-0
dc.relation.referencesBrochu, C., Halmeur, A., & Ouellette, M. (2004). The heat shock protein HSP70 and heat shock cognate protein HSC70 contribute to antimony tolerance in the protozoan parasite Leishmania. Cell Stress & Chaperones, 9(3), 294–303.
dc.relation.referencesBurza, S., Croft, S. L., & Boelaert, M. (2018). Leishmaniasis. The Lancet, 392, 951-970. doi: 10.1016/s0140-6736(18)31204-2.
dc.relation.referencesCamacho, E., González-de la Fuente, S., Rastrojo, A., Peiró-Pastor, R., Solana, J. C., Tabera, L., Gamarro, F., Carrasco-Ramiro, F., Requena, J. M., & Aguado, B. (2019). Complete assembly of the Leishmania donovani (HU3 strain) genome and transcriptome annotation. Scientific Reports, 9(1), 6127. https://doi.org/10.1038/s41598-019-42511-4
dc.relation.referencesCantacessi, C., Dantas-Torres, F., Nolan, M. J., & Otranto, D. (2015). The past, present, and future of Leishmania genomics and transcriptomics. Trends in Parasitology, 31(3), 100-108. https://doi.org/10.1016/j.pt.2014.12.012
dc.relation.referencesCastanys-Muñoz, E., Pérez-Victoria, J. M., Gamarro, F., & Castanys, S. (2008). Characterization of an ABCG-like transporter from the protozoan parasite Leishmania with a role in drug resistance and transbilayer lipid movement. Antimicrobial Agents and Chemotherapy, 52(10), 3573-3579. https://doi.org/10.1128/AAC.00562-08
dc.relation.referencesCastaño Rodríguez, M. (2020). Evaluación de la susceptibilidad a la anfotericina B de parásitos de Leishmania del subgénero Viannia con resistencia adquirida in vitro a miltefosina [Tesis de maestría, Universidad Nacional de Colombia]. Repositorio Institucional Universidad Nacional de Colombia.
dc.relation.referencesCastro, MdM., Cossio, A., Velasco, C., & Osorio, L. (2017). Risk factors for therapeutic failure to meglumine antimoniate and miltefosine in adults and children with cutaneous leishmaniasis in Colombia: A cohort study. PLoS Neglected Tropical Diseases, 11(4), e0005515. doi:10.1371/journal.pntd.0005515.
dc.relation.referencesChang, K. P., & McGwire, B. S. (2002). Molecular determinants and regulation of Leishmania virulence. Kinetoplastid Biology and Disease, 1(1), 1–7.
dc.relation.referencesChaudhuri, G., Chaudhuri, M., Pan, A., & Chang, K. P. (1989). Surface acid proteinase (gp63) of Leishmania mexicana: A metalloenzyme capable of protecting liposome-encapsulated proteins from phagolysosomal degradation by macrophages. Journal of Biological Chemistry, 264(13), 7483-7489.
dc.relation.referencesChen, D. Q., Kolli, B. K., Yadava, N., Lu, H. G., Gilman-Sachs, A., Peterson, D. A., & Chang, K. P. (2000). Episomal expression of specific sense and antisense mRNAs in Leishmania amazonensis: Modulation of gp63 level in promastigotes and their infection of macrophages in vitro. Infection and Immunity, 68(1), 80-86. https://doi.org/10.1128/IAI.68.1.80-86.2000
dc.relation.referencesClayton, C., & Shapira, M. (2007). Post-transcriptional regulation of gene expression in trypanosomes and leishmanias. Molecular & Biochemical Parasitology, 156(2), 93–101. https://doi.org/10.1016/j.molbiopara.2007.07.007
dc.relation.referencesCoelho, A. C., Boisvert, S., Mukherjee, A., Leprohon, P., Corbeil, J., & Ouellette, M. (2012). Multiple Mutations in Heterogeneous Miltefosine-Resistant Leishmania major Population as Determined by Whole Genome Sequencing. PLoS Neglected Tropical Diseases, 6(2), e1512. doi:10.1371/journal.pntd.0001512.
dc.relation.referencesCollett, C. F., Kitson, C., Baker, N., Steele-Stallard, H. B., Santrot, M. V., Hutchinson, S., Horn, D., & Alsford, S. (2019). Chemogenomic profiling of antileishmanial efficacy and resistance in the related kinetoplastid parasite Trypanosoma brucei. Antimicrobial Agents and Chemotherapy, 63(8), e00795-19. https://doi.org/10.1128/AAC.00795-19
dc.relation.referencesConesa, A., Götz, S., García-Gómez, J. M., Terol, J., Talón, M., & Robles, M. (2005). BLAST2GO: a universal tool for annotation, visualization and analysis in functional genomics research. Bioinformatics, 21: 3674-3676.
dc.relation.referencesCortés, L. A., & Fernández, J. J. (2008). Especies de Lutzomyia en un foco urbano de 112 leishmaniasis visceral y cutánea en el Carmen de Bolívar, Bolívar, Colombia. Biomédica, 28, 433-40.
dc.relation.referencesCoughlan, S., Taylor, A. S., Feane, E., Sanders, M., Schonian, G., Cotton, J. A., & Downing, T. (2018). Leishmania naiffi and Leishmania guyanensis reference genomes highlight genome structure and gene evolution in the Viannia subgenus. Royal Society open science,5(4), 172212.
dc.relation.referencesCroft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev. 2006; 19:111– 26. https://doi.org/10.1128/CMR.19.1.111-126.2006
dc.relation.referencesCruz, M. C., Souza-Melo, N., da Silva, C. V., Darocha, W. D., Bahia, D., Araujo, P. R., Teixeira, S. R., & Mortara, R. A. (2012). Trypanosoma cruzi: Role of delta-amastin on extracellular amastigote cell invasion and differentiation. PLoS ONE, 7(12), e51804. https://doi.org/10.1371/journal.pone.0051804
dc.relation.referencesCruz, M. L. (2014). Identificación de la especie de Leishmania productora de cuadros cutáneos y evaluación de la posible resistencia al antimoniato de meglumina, en una cohorte de pacientes con falla terapéutica al Glucantime [Tesis de maestría, Universidad Nacional de Colombia, Facultad de Medicina].
dc.relation.referencesCunha, J., Carrillo, E., Sánchez, C., Cruz, I., Moreno, J., & Cordeiro-da-Silva, A. (2013). Characterization of the biology and infectivity of Leishmania infantum viscerotropic and dermotropic strains isolated from HIV+ and HIV− patients in the murine model of visceral leishmaniasis. Parasites & Vectors, 6, 122.
dc.relation.referencesCuypers, B., Meysman, P., Erb, I., Bittremieux, W., Valkenborg, D., Baggerman, G., Mertens, I., Sundar, S., Khanal, B., Notredame, C., Dujardin, J.-C., Domagalska, M. A., & Laukens, K. (2022). Four-layer multi-omics reveals molecular responses to aneuploidy in Leishmania. PLOS Pathogens, 18(9), e1010848. https://doi.org/10.1371/journal.ppat.1010848
dc.relation.referencesDanecek, P., Bonfield, J. K., Liddle, J., Marshall, J., Ohan, V., Pollard, M. O., ... & Li, H. (2021). Twelve years of SAMtools and BCFtools. Gigascience, 10(2), giab008. https://doi.org/10.1093/gigascience/giab008
dc.relation.referencesDas, M., Saudagar, P., Sundar, S., & Dubey, V. K. (2013). Miltefosine-unresponsive Leishmania donovani has a greater ability than miltefosine-responsive L. donovani to 113 resist reactive oxygen species. FEBS Journal, 280(19), 4807-4815. https://doi.org/10.1111/febs.12453
dc.relation.referencesDenton, H., McGregor, J. C., & Coombs, G. H. (2004). Reduction of anti-leishmanial pentavalent antimonial drugs by a parasite-specific thiol-dependent reductase, TDR1. Biochemical Journal, 381(2), 405–412.
dc.relation.referencesDiotallevi, A., Buffi, G., Corbelli, G., Ceccarelli, M., Ortalli, M., Varani, S., Magnani, M., & Galluzzi, L. (2021). In vitro reduced susceptibility to pentavalent antimonials of a Leishmania infantum isolate from a human cutaneous leishmaniasis case in Central Italy. Microorganisms, 9(6), 1147. https://doi.org/10.3390/microorganisms9061147
dc.relation.referencesDoudna, J. A., & Charpentier, E. (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346, 1258096. https://doi.org/10.1126/science.1258096
dc.relation.referencesDowning, T., Imamura, H., Decuypere, S., Clark, T. G., Coombs, G. H., Cotton, J. A., Hilley, J. D., de Doncker, S., Maes, I., Mottram, J. C., Quail, M. A., Rijal, S., Sanders, M., Schönian, G., Stark, O., Sundar, S., Vanaerschot, M., Hertz-Fowler, C., Dujardin, J.-C., & Berriman, M. (2011). Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Genome Research, 21(12), 2143–2156. https://doi.org/10.1101/gr.123430.111
dc.relation.referencesDuitama, J., Quintero, J. C., Cruz, D. F., Quintero, C., Hubmann, G., Foulquié-Moreno, M. R., ... & Tohme, J. (2014). An integrated framework for discovery and genotyping of genomic variants from high-throughput sequencing experiments. Nucleic Acids Research, 42, e44.
dc.relation.referencesDujardin, J., Mannaert, A., Durrant, C., & Cotton, J. (2014). Mosaic aneuploidy in Leishmania: The perspective of whole genome sequencing. Trends in Parasitology, 30(12), 554–555. https://doi.org/10.1016/j.pt.2014.09.004
dc.relation.referencesDumetz, F., Imamura, H., Sanders, M., Seblova, V., Myskova, J., Pescher, P., Vanaerschot, M., Meehan, C. J., Cuypers, B., De Muylder, G., Späth, G. F., Bussotti, G., Vermeesch, J., Berriman, M., Cotton, J., Volf, P., Dujardin, J., & Domagalska, M. (2017). Modulation of aneuploidy in Leishmania donovani during adaptation to different in vitro and in vivo 114 environments and its impact on gene expression. mBio, 8. https://doi.org/10.1128/mBio.00599-17
dc.relation.referencesEfstathiou, A., & Smirlis, D. (2021). Leishmania protein kinases: Important regulators of the parasite life cycle and molecular targets for treating leishmaniasis. Microorganisms, 9(691). https://doi.org/10.3390/microorganisms9040691
dc.relation.referencesEmanuelsson, O., Nielsen, H., Brunak, S., & von Heijne, G. (2000). Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J Mol Biol, 300: 1005-1016.
dc.relation.referencesEngel, J. C., Ang, K. K. H., Chen, S., Arkin, M. R., McKerrow, J. H., et al. (2010). Image-based high-throughput drug screening targeting the intracellular stage of Trypanosoma cruzi, the agent of Chagas’ disease. Antimicrobial Agents and Chemotherapy, 54, 3326–3334.
dc.relation.referencesEspada, C. R., Albuquerque-Wendt, A., Hornillos, V., Gluenz, E., Coelho, A. C., & Uliana. R. B. (2021a). Ros3 (Lem3p/CDC50) Gene Dosage Is Implicated in Miltefosine Susceptibility in Leishmania (Viannia) braziliensis Clinical Isolates and in Leishmania (Leishmania) major. ACS Infectious Diseases, 7(4), 849-858. doi: 10.1021/acsinfecdis.0c00857.
dc.relation.referencesEspada, C. R., Quilles, J. C., Albuquerque-Wendt, A., Cruz, M. C., Beneke, T., Lorenzon, L. B., Gluenz, E., Cruz, A. K., & Uliana, S. R. B. (2021b). Effective Genome Editing in Leishmania (Viannia) braziliensis Stably Expressing Cas9 and T7 RNA Polymerase. Frontiers in Cellular and Infection Microbiology, 11, 772311. doi: 10.3389/fcimb.2021.772311.
dc.relation.referencesFernández, O. L., Diaz-Toro, Y., Ovalle, C., Valderrama, L., Muvdi, S., Rodriguez, I., Gomez, M. A., & Saravia, N. G. (2014). Miltefosine and Antimonial Drug Susceptibility of Leishmania Viannia Species and Populations in Regions of High Transmission in Colombia. PLoS Neglected Tropical Diseases, 8(5), e2871. doi:10.1371/journal.pntd.0002871.
dc.relation.referencesFernández, O., Díaz-Toro, Y., Valderrama, L., Ovalle, C., Valderrama, M., & otros. (2012). Novel approach to in vitro drug susceptibility assessment of clinical strains of Leishmania spp. Journal of Clinical Microbiology, 50(7), 2207–2211.
dc.relation.referencesFerreira, B. A., Coser, E. M., de la Roca, S., Aoki, J. I., Branco, N., Soares, G. H. C., Lima, M. I. S., & Coelho, A. C. (2024). Amphotericin B resistance in Leishmania amazonensis: In 115 vitro and in vivo characterization of a Brazilian clinical isolate. PLoS Neglected Tropical Diseases, 18(5), e0012175. https://doi.org/10.1371/journal.pntd.0012175
dc.relation.referencesFonseca, M.S., Comini, M.A., Resende, B.V., Santi, A.M.M., Zoboli, A.P., Moreira, D.S., & Murta, S.M.F. (2017). Ornithine decarboxylase or gamma-glutamylcysteine synthetase overexpression protects Leishmania (Vianna) guyanensis against antimony. Experimental Parasitology, 175, 36-43. doi: 10.1016/j.exppara.2017.02.001.
dc.relation.referencesFranco-Muñoz, C., Manjarrés-Estremor, M., & Ovalle-Bracho, C. (2018). Intraspecies differences in natural susceptibility to amphotericine B of clinical isolates of Leishmania subgenus Viannia. Plos one, 13(4), e0196247.
dc.relation.referencesFreitas-Mesquita, A. L., Dos-Santos, A. L. A., & Meyer-Fernandes, J. R. (2021). Involvement of Leishmania phosphatases in parasite biology and pathogeny. Frontiers in Cellular and Infection Microbiology, 11, 633146. https://doi.org/10.3389/fcimb.2021.633146
dc.relation.referencesFrézard, F., Demicheli, C., & Ribeiro, R. R. (2009). Pentavalent antimonials: new perspectives for old drugs. Molecules, 30,14(7), 2317-36. doi: 10.3390/molecules14072317.
dc.relation.referencesFyfe, P. K., Westrop, G. D., Silva, A. M., Coombs, G. H., & Hunter, W. N. (2012). Leishmania TDR1 structure, a unique trimeric glutathione transferase capable of deglutathionylation and antimonial prodrug activation. Proceedings of the National Academy of Sciences, 109(29), 11693–11698.
dc.relation.referencesGamarro, F., Sánchez-Cañete, M. P., & Castanys, S. (2013). Mechanisms of miltefosine resistance in Leishmania. In A. Ponte-Sucre (Ed.), Drug resistance in Leishmania parasites (pp. 351-379). Springer. https://doi.org/10.1007/978-3-7091-1125-3_17
dc.relation.referencesGonzalez-Garcia, L. N., Rodríguez-Guzmán, A. M., Vargas-León, C. M., Aponte, S., Bonilla-Valbuena, L. A., Matiz-González, J. M., Clavijo-Vanegas, A. M., Duarte-Olaya, G. A., Aguilar-Buitrago, C., Urrea, D. A., Duitama, J., & Echeverry, M. C. (2025). Genomic characterization of Leishmania (V.) braziliensis associated with antimony therapeutic failure and variable in vitro tolerance to amphotericin B. Scientific Reports, 15, 12973. https://doi.org/10.1038/s41598-025-19971-6
dc.relation.referencesGonzález-de la Fuente, S., Camacho, E., Peiró-Pastor, R., Rastrojo, A., Carrasco-Ramiro, F., Aguado, B., & Requena, J. M. (2018). Complete and de novo assembly of the Leishmania braziliensis (M2904) genome. Memórias do Instituto Oswaldo Cruz, 114, 116 e180438. https://doi.org/10.1590/0074-02760180438
dc.relation.referencesGonzález-de la Fuente, S., Peiró-Pastor, R., Rastrojo, A., Moreno, J., Carrasco-Ramiro, F., Requena, J. M., & Aguado, B. (2017). Resequencing of the Leishmania infantum (strain JPCM5) genome and de novo assembly into 36 contigs. Scientific Reports, 7(1), 18050. https://doi.org/10.1038/s41598-017-18374-y
dc.relation.referencesGossage, S. M., Rogers, M. E., & Bates, P. A. (2003). Two separate growth phases during the development of Leishmania in sand flies: Implications for understanding the life cycle. International Journal of Parasitology, 33(10), 1027-1034. https://doi.org/10.1016/s0020-7519(03)00142-5.
dc.relation.referencesGourbal, B., Sonuc, N., Bhattacharjee, H., Legare, D., Sundar, S., Ouellette, M., … Mukhopadhyay, R. (2004). Drug Uptake and Modulation of Drug Resistance in Leishmania by an Aquaglyceroporin. Journal of Biological Chemistry, 279(30), 31010–31017. doi:10.1074/jbc.m403959200.
dc.relation.referencesGuatibonza Carreño, A. M. (2019). Evaluación de la susceptibilidad intracelular de Leishmania braziliensis a antimoniales liposomales y Glucantime® en macrófagos humanos de línea celular U-937 in vitro [Tesis de maestría, Universidad Manuela Beltrán]. Universidad Manuela Beltrán.
dc.relation.referencesGuimond, C., Trudel, N., Brochu, C., Marquis, N., El Fadili, A., Peytavi, R., Briand, G., Richard, D., Messier, N., & Papadopoulou, B. (2003). Modulation of gene expression in Leishmania drug-resistant mutants as determined by targeted DNA microarrays. Nucleic Acids Research, 31(20), 5886–5896. https://doi.org/10.1093/nar/gkg789
dc.relation.referencesHenao, H. H., Osorio, Y., Saravia, N. G., Gómez, A., & Travi, B. (2004). Eficacia y toxicidad de los antimoniales pentavalentes (Glucantime® y Pentostam®) en un modelo animal de leishmaniasis cutánea americana: aplicación de la luminometría. Biomédica, 24, 393-402.
dc.relation.referencesHerrera, G., Teherán, A., Pradilla, I., Vera, M., & Ramírez, J. D. (2018). Geospatial-temporal distribution of Tegumentary Leishmaniasis in Colombia (2007-2016). PLoS Neglected Tropical Diseases, 12(4),e0006419. https://doi.org/10.1371/journal.pntd.0006419.
dc.relation.referencesHersel, U., Dahmen, C., & Kessler, H. (2003). RGD modified polymers: Biomaterials for stimulated cell adhesion and beyond. Biomaterials, 24(24), 4385–4415. 117 https://doi.org/10.1016/s0142-9612(03)00343-0
dc.relation.referencesHirve, S., Boelaert, M., Matlashewski, G., Mondal, D., Arana, B., Kroeger, A., & Olliaro, P. (2016). Transmission dynamics of visceral leishmaniasis in the Indian subcontinent—A systematic literature review. PLoS Neglected Tropical Diseases, 10(8), e0004896. https://doi.org/10.1371/journal.pntd.0004896
dc.relation.referencesHoyos, J., Rosales-Chilama, M., León, C., González, C., & Gómez, M. A. (2022). Sequencing of hsp70 for discernment of species from the Leishmania (Viannia) guyanensis complex from endemic areas in Colombia. Parasites & Vectors, 3, 15(1), 406. doi: 10.1186/s13071-022-05438-w.
dc.relation.referencesIbarra-Meneses, A. V., Corbeil, A., Wagner, V., Beaudry, F., do Monte-Neto, R. L., & Fernandez-Prada, C. (2022). Exploring direct and indirect targets of current antileishmanial drugs using a novel thermal proteomics profiling approach. Frontiers in Cellular and Infection Microbiology, 12, 954144. https://doi.org/10.3389/fcimb.2022.954144
dc.relation.referencesINS (Instituto Nacional de Salud). (2024). Boletín Epidemiológico Semanal: Semana epidemiológica 24. Recuperado de: https://www.ins.gov.co/BibliotecaDigital/2024-boletin-epidemiologico-semana-25.pdf
dc.relation.referencesIshemgulova, A., Hlavacova, J., Majerova, K., Butenko, A., Lukes, J., Votypka, J., Volf, P., & Yurchenko, V. (2018). CRISPR/Cas9 in Leishmania mexicana: A case study of LmxBTN1. PLOS ONE, 13(2), e0192723. https://doi.org/10.1371/journal.pone.0192723
dc.relation.referencesIsnard, A., Shio, M. T., & Olivier, M. (2012). Impact of Leishmania metalloprotease GP63 on macrophage signaling. Frontiers in Cellular and Infection Microbiology, 2, 72. https://doi.org/10.3389/fcimb.2012.00072
dc.relation.referencesKane, M. M., & Mosser, D. M. (2001). The role of IL-10 in promoting disease progression in leishmaniasis. Journal of Immunology, 166(2), 1141–1147. https://doi.org/10.4049/jimmunol.166.2.1141
dc.relation.referencesKelley, L. A., & Sternberg, M.J. (2009). Protein structure prediction on the Web: a case study using the Phyre server. Nat Protoc, 4: 363-371.
dc.relation.referencesKip, A. E., Schellens, J. H. M., Beijnen, J. H., & Dorlo, T. P. C. (2018). Clinical 118 pharmacokinetics of systemically administered antileishmanial drugs. Clinical Pharmacokinetics, 57(2), 151–176. https://doi.org/10.1007/s40262-017-0570-0
dc.relation.referencesKrogh, A., Larsson, B., von Heijne, G., & Sonnhammer, E. L. (2001). Predicting transmembrane protein topology with a hidden Markov model: Application to complete genomes. Journal of Molecular Biology, 305, 567–580.
dc.relation.referencesKryazhimskiy, S., & Plotkin, J. B. (2008). The population genetics of dN/dS. PLoS Genetic, 4(12): e1000304. doi: 10.1371/journal.pgen.1000304.
dc.relation.referencesKumar, A., Das, S., Purkait, B., Sardar, A. H., Ghosh, A. K., Dikhit, M. R., & Das, P. (2014). Ascorbate peroxidase, a key molecule regulating amphotericin B resistance in clinical isolates of Leishmania donovani. Antimicrobial Agents and Chemotherapy, 58(10), 6172–6184. https://doi.org/10.1128/AAC.02834-14
dc.relation.referencesKumari, S., Kumar, V., Tiwari, R. K., Ravidas, V., Pandey, K., & Kumar, A. (2022). Amphotericin B: A drug of choice for Visceral Leishmaniasis. Acta Tropica, 235, 106661. https://doi.org/10.1016/j.actatropica.2022.106661
dc.relation.referencesLachaud, L., Bourgeois, N., Kuk, N., Morelle, C., Crobu, L., Merlin, G., Bastien, P., Pagès, M., & Sterkers, Y. (2014). Constitutive mosaic aneuploidy is a unique genetic feature widespread in the Leishmania genus. Microbes and Infection, 16(1), 61-66. https://doi.org/10.1016/j.micinf.2013.09.005
dc.relation.referencesLaffitte, M. C. N., Leprohon, P., Papadopoulou, B., & Ouellette, M. (2016). Plasticity of the Leishmania genome leading to gene copy number variations and drug resistance. F1000Research, 5, 2350. doi: 10.12688/f1000research.9218.1.
dc.relation.referencesLaffitte, M. C., Genois, M. M., Mukherjee, A., Légaré, D., Masson, J. Y., & Ouellette, M. (2014). Formation of linear amplicons with inverted duplications in Leishmania requires the MRE11 nuclease. PLoS Genetics, 10(12), e1004805. https://doi.org/10.1371/journal.pgen.1004805
dc.relation.referencesLamprea-Barragán, L. X. (2019). Descripción del patrón de susceptibilidad in vitro de Leishmania amazonensis a antimoniato de meglumina en pacientes colombianos [Tesis de pregrado, Pontificia Universidad Javeriana, Facultad de Ciencias]. Bogotá, D.C.
dc.relation.referencesLander, N., & Chiurillo, M. A. (2019). State-of-the-art CRISPR/Cas9 technology for genome 119 editing in trypanosomatids. Journal of Eukaryotic Microbiology, 66(6), 981–991. https://doi.org/10.1111/jeu.12747
dc.relation.referencesLangmead, B., & Salzberg, S. (2012). Fast gapped-read alignment with Bowtie 2. Nature Methods, 9, 357–359. https://doi.org/10.1038/nmeth.1923
dc.relation.referencesLantorno, S. A., Durrant, C., Khan, A., Sanders, M. J., Beverley, S. M., Warren, W. C., Berriman, M., Sacks, D. L., Cotton, J. A., & Grigg, M. E. (2017). Gene expression in Leishmania is regulated predominantly by gene dosage. mBio, 8(5), e01393-17. https://doi.org/10.1128/mBio.01393-17
dc.relation.referencesLeprohon, P., Fernandez-Prada, C., Gazanion, É., Monte-Neto, R., & Ouellette, M. (2015). Drug resistance analysis by next generation sequencing in Leishmania. International Journal for Parasitology: Drugs and Drug Resistance, 5(1), 26–35. https://doi.org/10.1016/j.ijpddr.2014.12.001
dc.relation.referencesLeprohon, P., Légaré, D., Raymond, F., Madore, É., Hardiman, G., Corbeil, J., & Ouellette, M. (2009). Gene expression modulation is associated with gene amplification, supernumerary chromosomes and chromosome loss in antimony-resistant Leishmania infantum. Nucleic Acids Research, 37(5), 1387–1399. https://doi.org/10.1093/nar/gkn1069
dc.relation.referencesLi, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., & Durbin, R. (2009). The Sequence alignment/map (SAM) format and SAMtools. Bioinformatics, 25: 2078-9.
dc.relation.referencesLlanes, A., Cruz, G., Morán, M., Vega, C., Pineda, V. J., Ríos, M., Penagos, H., Suárez, J. A., Saldaña, A., Lleonart, R., & Restrepo, C. M. (2022). Genomic diversity and genetic variation of Leishmania panamensis within its endemic range. Infection, Genetics and Evolution, 103, 105342. https://doi.org/10.1016/j.meegid.2022.105342
dc.relation.referencesLlanes, A., Restrepo, C. M., Del Vecchio, G., Anguizola, F. J., & Lleonart, R. (2015). The genome of Leishmania panamensis: Insights into genomics of the L. (Viannia) subgenus. Scientific Reports, 5, 8550. https://doi.org/10.1038/srep08550
dc.relation.referencesMadusanka, R. K., Silva, H., & Karunaweera, N. D. (2022). Treatment of Cutaneous Leishmaniasis and Insights into Species-Specific Responses: A Narrative Review. Infectious Diseases and Therapy, 11, 695-711.
dc.relation.referencesMaltezou, H. C. (2010). Drug resistance in visceral leishmaniasis. Journal of Biomedicine and Biotechnology, 2010, Article 617521. https://doi.org/10.1155/2010/617521
dc.relation.referencesMarquis, N., Gourbal, B., Rosen, B. P., Mukhopadhyay, R., & Ouellette, M. (2005). Modulation in aquaglyceroporin AQP1 gene transcript levels in drug-resistant Leishmania. Molecular Microbiology, 57(6), 1690–1699. https://doi.org/10.1111/j.1365-2958.2005.04782.x
dc.relation.referencesMasne, T., Kumar, D., & Bansode, D. (2024). A review of leishmaniasis: Current knowledge and future directions of heterocyclic molecules. Exploratory Drug Science, 2, 508–539. https://doi.org/10.37349/eds.2024.00059
dc.relation.referencesMcCall, L.-I., Aroussi, A. E., Choi, J. Y., Vieira, D. F., Muylder, G. D., Johnston, J. B., et al. (2015). Targeting ergosterol biosynthesis in Leishmania donovani: Essentiality of sterol 14α-demethylase. PLoS Neglected Tropical Diseases, 9(3), e0003588. https://doi.org/10.1371/journal.pntd.0003588
dc.relation.referencesMéndez-Bejarano, C. P., Correa-Cárdenas, C. A., Pérez-Rico, J. J., Romero-Barbosa, Y. A., & Rodríguez-Angarita, O. (2020). Carga parasitaria de Leishmania spp. en personal militar colombiano con leishmaniasis cutánea: estudio de caso. Revista Científica General José María Córdova, 18(29), 237-266. doi: 10.21830/19006586.515.
dc.relation.referencesMishra, J., & Singh, S. (2013). Miltefosine resistance in Leishmania donovani involves suppression of oxidative stress-induced programmed cell death. Experimental Parasitology, 135(2), 397-406. https://doi.org/10.1016/j.exppara.2013.08.004
dc.relation.referencesMoncada-Diaz, M. J., Rodríguez-Almonacid, C. C., Quiceno-Giraldo, E., Khuong, F. T. H., Muskus, C., & Karamysheva, Z. N. (2024). Molecular mechanisms of drug resistance in Leishmania spp. Pathogens, 13(10), 835. https://doi.org/10.3390/pathogens13100835
dc.relation.referencesMongan, T. P., Ganapasam, S., Hobbs, S. B., & Seyfang, A. (2004). Substrate specificity of the Leishmania donovani myo-inositol transporter: Critical role of inositol C-2, C-3 and C-5 hydroxyl groups. Molecular and Biochemical Parasitology, 135(1), 133-141. https://doi.org/10.1016/j.molbiopara.2004.01.015
dc.relation.referencesMontalvo, A. M., Fraga, J., Montano, I., Monzote, L., Van der Auwera, G., Marín, M., & Muskus, C. (2016). Identificación molecular con base en el gen hsp70 de aislamientos clínicos de Leishmania spp. en Colombia. Biomédica, 36(Suppl. 1), 37-44. https://doi.org/10.7705/biomedica.v36i2.2688
dc.relation.referencesMonte-Neto, R., Laffitte, M. C. N., Leprohon, P., Reis, P., Frézard, F., & Ouellette, M. (2015). Intrachromosomal amplification, locus deletion and point mutation in the Aquaglyceroporin AQP1 gene in antimony resistant Leishmania (Viannia) guyanensis. PLoS Neglected Tropical Diseases, 9(2), 1–24.
dc.relation.referencesMoody, T. N., Ochieng, J., & Villalta, F. (2000). Novel mechanism that Trypanosoma cruzi uses to adhere to the extracellular matrix mediated by human galectin-3. FEBS Letters, 470, 305–308. https://doi.org/10.1016/s0014-5793(00)01347-8
dc.relation.referencesMota, W. J. S., Guedes, B. N., Jain, S., Silva, A. M., Santos, A. L. S., Branquinha, M. H., & Dos Santos, A. L. S. (2024). Classical and innovative drugs for the treatment of Leishmania infections. Discover Public Health, 21(1), 122. https://doi.org/10.1186/s12982-024-00247-1
dc.relation.referencesMukherjee, A., Boisvert, S., Monte-Neto, R. L., Coelho, A. C., Raymond, F., Mukhopadhyay, R., Corbeil, J., & Ouellette, M. (2013). Telomeric gene deletion and intrachromosomal amplification in antimony-resistant Leishmania. Molecular Microbiology, 88(1), 189–202. https://doi.org/10.1111/mmi.12178
dc.relation.referencesMukherjee, A., Padmanabhan, P. K., Singh, S., Roy, G., Girard, I., Chatterjee, M., Ouellette, M., & Madhubala, R. (2007). Role of ABC transporter MRPA, γ-glutamylcysteine synthetase and ornithine decarboxylase in natural antimony-resistant isolates of Leishmania donovani. Journal of Antimicrobial Chemotherapy, 59, 204–211.
dc.relation.referencesMwenechanya, R., Kovářová, J., Dickens, N. J., Mudaliar, M., Herzyk, P., Vincent, I. M., Weidt, S. K., Burgess, K. E., Burchmore, R. J. S., Pountain, A. W., Smith, T. K., Creek, D. J., Kim, D.-H., Lepesheva, G. I., & Barrett, M. P. (2017). Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana. PLoS Neglected Tropical Diseases, 11(6), e0005649. https://doi.org/10.1371/journal.pntd.0005649
dc.relation.referencesNatera, S., Machuca, C., Padron-Nieves, M., Romero, A., Diaz, E., & Ponte-Sucre, A. (2007). Leishmania spp.: Proficiency of drug-resistant parasites. International Journal of Antimicrobial Agents, 29(6), 637–642.
dc.relation.referencesNational Center for Biotechnology Information. (1988). NCBI [Database]. National Library of Medicine (US). https://www.ncbi.nlm.nih.gov/
dc.relation.referencesNde, P. N., Lima, M. F., Johnson, C. A., et al. (2012). Regulation and use of the extracellular 122 matrix by Trypanosoma cruzi during early infection. Frontiers in Immunology, 3, 337. https://doi.org/10.3389/fimmu.2012.00337
dc.relation.referencesNing, Y., Frankfater, C., Hsu, F. F., Soares, R. P., Cardoso, C. A., Nogueira, P. M., Lander, N. M., Docampo, R., & Zhang, K. (2020). Lathosterol oxidase (sterol C-5 desaturase) deletion confers resistance to amphotericin B and sensitivity to acidic stress in Leishmania major. mSphere, 5(4), e00380-20. https://doi.org/10.1128/mSphere.00380-20
dc.relation.referencesObonaga, R., Fernández, O. L., Valderrama, L., Rubiano, L. C., Castro, M. del M., Barrera, M. C., Gomez, M. A., & Gore Saravia, N. (2014). Treatment failure and miltefosine susceptibility in dermal leishmaniasis caused by Leishmania subgenus Viannia species. Antimicrobial Agents and Chemotherapy, 58(1), 144-152. https://doi.org/10.1128/AAC.01023-13
dc.relation.referencesOliaee, R. T., Sharifi, I., Afgar, A., Kareshk, A. T., Asadi, A., Heshmatkhah, A., et al. (2018). Unresponsiveness to meglumine antimoniate in anthroponotic cutaneous leishmaniasis field isolates: Analysis of resistance biomarkers by gene expression profiling. Tropical Medicine & International Health, 23(6), 622–633. https://doi.org/10.1111/tmi.13057
dc.relation.referencesOlivier, M., Atayde, V. D., Isnard, A., Hassani, K., & Shio, M. T. (2012). Leishmania virulence factors: Focus on the metalloprotease GP63. Microbes and Infection, 14(15), 1377-1389. https://doi.org/10.1016/j.micinf.2012.05.014
dc.relation.referencesOPS (Organización Panamericana de la Salud). (2019). Manual de procedimientos para vigilancia y control de las leishmaniasis en las Américas. Washington, D. C.
dc.relation.referencesOPS (Organización Panamericana de la Salud). (2023). Manual de procedimientos para vigilancia y control de las leishmaniasis en las Américas. Washington, D. C.
dc.relation.referencesPapadopoulou, B., Ouellette, M., Laffitte, M. C. N., & Leprohon, P. (2016). Plasticity of the Leishmania genome leading to gene copy number variations and drug resistance. F1000Research, 5, 1–10. https://doi.org/10.12688/f1000research.9218.1
dc.relation.referencesPatiño, L. H. (2019). Genómica y transcriptómica comparativa de cepas de Leishmania de Colombia (Tesis doctoral). Universidad Nuestra Señora del Rosario, Bogotá, Colombia.
dc.relation.referencesPatiño, L. H., Imamura, H., Cruz-Saavedra, L., Pavía, P., Muskus, C., Méndez, C., Dujardin, 123 J.-C., & Ramírez, J. D. (2019). Major changes in chromosomal somy, gene expression and gene dosage driven by SbIII in Leishmania braziliensis and Leishmania panamensis. Scientific Reports, 9(1), 9485. https://doi.org/10.1038/s41598-019-45538-9
dc.relation.referencesPatiño, L. H., Mendez, C., Rodriguez, O., Romero, Y., Velandia, D., Alvarado, M.,…Ramírez, J. D. (2017). Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army. PLoS Neglected Tropical Diseases, 11(8), e0005876. https://doi.org/10.1371/journal.pntd.0005876.
dc.relation.referencesPatiño, L. H., Muñoz, M., Pavia, P., Muskus, C., Shaban, M., Paniz-Mondolfi, A., & Ramírez, J. D. (2022). Filling the gaps in Leishmania naiffi and Leishmania guyanensis genome plasticity. G3: Genes|Genomes|Genetics, 12(1), jkab377. https://doi.org/10.1093/g3journal/jkab377
dc.relation.referencesPeacock, C. S., Seeger, K., Harris, D., Murphy, L., Ruiz, J. C., Quail, M. A., ... & Berriman, M. (2007). Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nature Genetics, 39(7), 839–847. https://doi.org/10.1038/ng2053
dc.relation.referencesPereira, L. O. R., Sousa, C. S., Ramos, H. C. P., Torres-Santos, E. C., Pinheiro, L. S., Alves, M. R., Cuervo, P., Romero, G. A. S., Boité, M. C., Porrozzi, R., & Cupolillo, E. (2021). Insights from Leishmania (Viannia) guyanensis in vitro behavior and intercellular communication. Parasites & Vectors, 14(1), 556. https://doi.org/10.1186/s13071-021-05057-x
dc.relation.referencesPérez-Cordero, J.-J., Sánchez-Suárez, J., & Delgado, G. (2011). Use of a fluorescent stain for evaluating in vitro infection with Leishmania panamensis. Experimental Parasitology, 129(1), 31–35. https://doi.org/10.1016/j.exppara.2011.05.022
dc.relation.referencesPérez-Franco, J. E., Cruz-Barrera, M. L., Robayo, M. L., Lopez, M. C., Daza, C. D., Bedoya A., …Echeverry. (2016). Clinical and Parasitological Features of Patients with American Cutaneous Leishmaniasis that Did Not Respond to Treatment with Meglumine Antimoniate. PLoS Neglected Tropical Diseases, 10(5), e0004739. doi:10.1371/journal.pntd.0004739.
dc.relation.referencesPérez-Victoria, F. J., Sanchez-Canete, M. P., Castanys, S., & Gamarro, F. (2006). Phospholipid translocation and miltefosine potency require both L. donovani miltefosine transporter and the new protein LdRos3 in Leishmania parasites. Journal of Biological 124 Chemistry, 281(33), 23766-23775. https://doi.org/10.1074/jbc.M605635200
dc.relation.referencesPetersen, T.N., Brunak, S., von Heijne, G., & Nielsen, H. (2011). SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods, 8: 785-786.
dc.relation.referencesPiel, L., Rajan, K. S., Bussotti, G., Varet, H., Legendre, R., Proux, C., Douché, T., Giai-Gianetto, Q., Chaze, T., Vojtkova, B., Gordon-Bar, N., Doniger, T., Cohen-Chalamish, S., Rengaraj, P., Besse, C., Boland, A., Sadlova, J., Deleuze, J.-F., Matondo, M., ... & Späth, G. F. (2021). Genome-wide adaptive evolution in Leishmania: Impact on virulence and host adaptation. bioRxiv. https://doi.org/10.1101/2021.03.22.436378
dc.relation.referencesPonte-Sucre, A., Gamarro, F., Dujardin, J. C., Barrett, M. P., Lopez-Velez, R., Garcia-Hernandez, R., Pountain, A. W., Mwenechanya, R., & Papadopoulou, B. (2017). Drug resistance and treatment failure in leishmaniasis: A 21st century challenge. PLoS Neglected Tropical Diseases, 11(12), e0006052. https://doi.org/10.1371/journal.pntd.0006052
dc.relation.referencesPourshafie, M., Morand, S., Virion, A., Rakotomanga, M., Dupuy, C., & Loiseau, P. M. (2004). Cloning of S-adenosyl-L-methionine:C-24-Δ-sterol-methyltransferase (ERG6) from Leishmania donovani and characterization of mRNAs in wild-type and amphotericin B-resistant promastigotes. Antimicrobial Agents and Chemotherapy, 48(7), 2409–2414. https://doi.org/10.1128/AAC.48.7.2409-2414.2004
dc.relation.referencesPurkait, B., Kumar, A., Nandi, N., Sardar, A. H., Das, S., Kumar, S., Pandey, K., Ravidas, V., Kumar, M., De, T., & Das, P. (2012). Mechanism of amphotericin B resistance in clinical isolates of Leishmania donovani. Antimicrobial Agents and Chemotherapy, 56(2), 1031–1041. https://doi.org/10.1128/AAC.00030-11
dc.relation.referencesRakotomanga, M., Saint-Pierre-Chazalet, M., & Loiseau, P. M. (2005). Alteration of fatty acid and sterol metabolism in miltefosine-resistant Leishmania donovani promastigotes and consequences for drug-membrane interactions. Antimicrobial Agents and Chemotherapy, 49(7), 2677-2686. https://doi.org/10.1128/AAC.49.7.2677-2686.2005
dc.relation.referencesRamírez, J., Hernández, C., León, C. Ayala, M. S., Flórez, C., & González, C. (2016). Taxonomy, diversity, temporal and geographical distribution of Cutaneous Leishmaniasis in Colombia: A retrospective study. Scientific Reports, 6, 28266. doi: 10.1038/srep28266.
dc.relation.referencesReal, F., Vidal, R. O., Carazzolle, M. F., Mondego, J. M., Costa, G. G., Herai, R. H., Würtele, 125 M., de Carvalho, L. M., Carmona e Ferreira, R., Mortara, R. A., Barbiéri, C. L., Mieczkowski, P., da Silveira, J. F., Briones, M. R., Pereira, G. A., & Bahia, D. (2013). The genome sequence of Leishmania (Leishmania) amazonensis: Functional annotation and extended analysis of gene models. DNA Research, 20(6), 567-581. https://doi.org/10.1093/dnares/dst031
dc.relation.referencesReckenfelderbäumer, N., Lüdemann, H., Schmidt, H., Steverding, D., & Krauth-Siegel, R. L. (2000). Identification and functional characterization of thioredoxin from Trypanosoma brucei brucei. Journal of Biological Chemistry, 275(11), 7547-7552. https://doi.org/10.1074/jbc.275.11.7547
dc.relation.referencesReis-Cunha, J. L., Valdivia, H. O., & Bartholomeu, D. C. (2018). Gene and chromosomal copy number variations as an adaptive mechanism towards a parasitic lifestyle in trypanosomatids. Current Genomics, 19(2), 87-97. https://doi.org/10.2174/1389202918666170911161311
dc.relation.referencesRestrepo, C. M., Llanes, A., Cedeño, E. M., Chang, J. H., Álvarez, J., Ríos, M., et al. (2019). Environmental conditions may shape the patterns of genomic variations in Leishmania panamensis. Genes, 10(11), 838.
dc.relation.referencesRijal, S., Ostyn, B., Uranw, S., Rai, K., Bhattarai, N. R., Dorlo, T. P., Beijnen, J. H., Vanaerschot, M., Decuypere, S., Dhakal, S. S., Das, M. L., Karki, P., Singh, R., Boelaert, M., & Dujardin, J. C. (2013). Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance. Clinical Infectious Diseases, 56(11), 1530–1538.
dc.relation.referencesRochette, A., McNicoll, F., Girard, J., Breton, M., Leblanc, E., Bergeron, M. G., & Papadopoulou, B. (2005). Characterization and developmental gene regulation of a large gene family encoding amastin surface proteins in Leishmania spp. Molecular and Biochemical Parasitology, 140(2), 205-220. https://doi.org/10.1016/j.molbiopara.2005.01.006
dc.relation.referencesRodríguez Guzmán, A. M. (2024). Análisis genómico y evolutivo de aislados clínicos de Leishmania (Viannia) braziliensis procedentes de zonas endémicas de Colombia asociado al estudio de los mecanismos de susceptibilidad a anfotericina B (AMB) [Tesis de maestría, Universidad del Tolima]. Universidad del Tolima, Repositorio Institucional.
dc.relation.referencesRodríguez-Barraquer, I., Gongora, R., Prager, M., Pacheco, R., Montero, L. M., Navas, A…Saravia, N. (2008). Etiologic agent of an epidemic of cutaneous leishmaniasis in Tolima, Colombia. The American Society of Tropical Medicine and Hygiene, 78(2), 276–82.
dc.relation.referencesRogers, M. B., Hilley, J. D., Dickens, N. J., Wilkes, J., Bates, P. A., Depledge, D. P., Harris, D., Her, Y., Herzyk, P., Imamura, H., Otto, T. D., Sanders, M., Seeger, K., Dujardin, J. C., Berriman, M., Smith, D. F., Hertz-Fowler, C., & Mottram, J. C. (2011). Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania. Genome Research, 21(12), 2129-2142. https://doi.org/10.1101/gr.122945.111
dc.relation.referencesRogers, M., Downing, T., Smith, B., Imamura, H., Sanders, M., Svobodová, M., Volf, P., Berriman, M., Cotton, J., & Smith, D. (2014). Genomic confirmation of hybridisation and recent inbreeding in a vector-isolated Leishmania population. PLoS Genetics, 10(1), e1004092. https://doi.org/10.1371/journal.pgen.1004092
dc.relation.referencesRowley, J. A., & Mooney, D. J. (2002). Alginate type and RGD density control myoblast phenotype. Journal of Biomedical Materials Research, 60, 217–223.
dc.relation.referencesRStudio Team. (2020). RStudio: Integrated development for R [Software]. RStudio, PBC. http://www.rstudio.com/
dc.relation.referencesRugani, J. N., Quaresma, P. F., Gontijo, C. F., Soares, R. P., & Monte-Neto, R. L. (2018). Intraspecies susceptibility of Leishmania (Viannia) braziliensis to antileishmanial drugs: Antimony resistance in human isolates from atypical lesions. Biomedicine & Pharmacotherapy, 108, 1170–1180.
dc.relation.referencesSaint-Pierre-Chazalet, M., Ben Brahim, M., Le Moyec, L., Bories, C., Rakotomanga, M., & Loiseau, P. M. (2009). Membrane sterol depletion impairs miltefosine action in wild-type and miltefosine-resistant Leishmania donovani promastigotes. Journal of Antimicrobial Chemotherapy, 64(5), 993-1001. https://doi.org/10.1093/jac/dkp308
dc.relation.referencesSalari, S., Bamorovat, M., Sharifi, I., & Almani, P. G. N. (2022). Global distribution of treatment resistance gene markers for leishmaniasis. Journal of Clinical Laboratory Analysis, 36(8), e24599. https://doi.org/10.1002/jcla.24599
dc.relation.referencesSalgado-Almario, J., Hernández, C. A., & Ovalle-Bracho, C. (2019). Distribución geográfica de 127 las especies de Leishmania en Colombia, 1985-2017. Biomédica, 39(2), 278-290. https://doi.org/10.7705/biomedica.v39i3.4312
dc.relation.referencesSánchez-Cañete, M. P., Carvalho, L., Pérez-Victoria, F. J., Gamarro, F., & Castanys, S. (2009). Low plasma membrane expression of the miltefosine transport complex renders Leishmania braziliensis refractory to the drug. Antimicrobial Agents and Chemotherapy, 53(4),1305-13. doi: 10.1128/AAC.01694-08.
dc.relation.referencesSánchez-Suárez, J., Bernal, F. A., & Coy-Barrera, E. (2020). Colombian contributions fighting leishmaniasis: A systematic review on antileishmanials combined with chemoinformatics analysis. Molecules, 25(23), 5704. https://doi.org/10.3390/molecules25235704
dc.relation.referencesSantana, J. M., Grellier, P., Schrével, J., & Teixeira, A. R. (1997). A Trypanosoma cruzi-secreted 80 kDa proteinase with specificity for human collagen types I and IV. Biochemical Journal, 325(Pt 1), 129–137. https://doi.org/10.1042/bj3250129
dc.relation.referencesSaravia, N., Fernandez, O., & Díaz, Y. (2011). Susceptibility of clinical strains of Leishmania to pentavalent antimony and Miltefosine: Challenges and oppotunities. Biomédica, 31(sup.3), 3-315.
dc.relation.referencesSarkar, A., Khan, Y. A., Laranjeira-Silva, M. F., & Andrews, N. W. (2018). Quantification of intracellular growth inside macrophages is a fast and reliable method for assessing the virulence of Leishmania parasites. Journal of Visualized Experiments, e57486.
dc.relation.referencesSasidharan, S., & Saudagar, P. (2021). Leishmaniasis: Where are we and where are we heading? Parasitology Research, 120(5), 1541-1554. https://doi.org/10.1007/s00436-021-07139-2
dc.relation.referencesSchmieder, R., & Edwards, R. (2011). Quality control and preprocessing of metagenomic datasets. Bioinformatics, 27(6), 863–864. https://doi.org/10.1093/bioinformatics/btr026
dc.relation.referencesSeay, M. B., Heard, P. L., & Chaudhuri, G. (1996). Surface Zn-proteinase as a molecule for defense of Leishmania mexicana amazonensis promastigotes against cytolysis inside macrophage phagolysosomes. Infection and Immunity, 64(12), 5129-5137. https://doi.org/10.1128/iai.64.12.5129-5137.1996
dc.relation.referencesSeifert, K., Pérez-Victoria, F. J., Stettler, M., Sanchez-Canete, M. P., Castanys, S., & Gamarro, F. (2007). Inactivation of the miltefosine transporter, LdMT, causes miltefosine 128 resistance that is conferred to the amastigote stage of Leishmania donovani and persists in vivo. International Journal of Antimicrobial Agents, 30(3), 229-235. https://doi.org/10.1016/j.ijantimicag.2007.05.007
dc.relation.referencesSereno, D., Harrat, Z., & Eddaikra, N. (2019). Meta-analysis and discussion on challenges to translate Leishmania drug resistance phenotyping into the clinic. Acta Tropica, 191, 204–211.
dc.relation.referencesSharma, R., Avendaño Rangel, F., Reis-Cunha, J. L., Marques, L. P., Figueira, C. P., Borba, P. B., Viana, S. M., Beneke, T., Bartholomeu, D. C., & de Oliveira, C. I. (2022). Targeted deletion of Centrin in Leishmania braziliensis using CRISPR-Cas9-based editing. Frontiers in Cellular and Infection Microbiology, 11, 790418. https://doi.org/10.3389/fcimb.2021.790418
dc.relation.referencesShirzadi, M. R. (2019). Liposomal amphotericin B: A review of its properties, function, and use for treatment of cutaneous leishmaniasis. Research and Reports in Tropical Medicine, 10, 11–18. https://doi.org/10.2147/RRTM.S160812
dc.relation.referencesSilverman, J. M., Chan, S. K., Robinson, D. P., Dwyer, D. M., Nandan, D., Foster, L. J., & Reiner, N. E. (2008). Proteomic analysis of the secretome of Leishmania donovani. Genome Biology, 9(2), R35. https://doi.org/10.1186/gb-2008-9-2-r35
dc.relation.referencesSinha, M., Jagadeesan, R., Kumar, N., Saha, S., Kothandan, G., & Kumar, D. (2022). In-silico studies on myo-inositol-1-phosphate synthase of Leishmania donovani in search of anti-leishmaniasis. Journal of Biomolecular Structure and Dynamics, 40(8), 3371-3384. https://doi.org/10.1080/07391102.2020.1847194
dc.relation.referencesSollelis, L., Ghorbal, M., MacPherson, C. R., Martins, R. M., Kuk, N., Crobu, L., Bastien, P., Scherf, A., Lopez-Rubio, J. J., & Sterkers, Y. (2015). First efficient CRISPR-Cas9-mediated genome editing in Leishmania parasites. Cellular Microbiology, 17(10), 1405–1412. https://doi.org/10.1111/cmi.12456
dc.relation.referencesSoto, J., Toledo, J., Vega, J., & Berman, J. (2005). Short report: efficacy of pentavalent antimony for treatment of colombian cutaneous leishmaniasis. American Journal of 129 Tropical Medicine and Hygiene, 72(4), 421-2.
dc.relation.referencesSteinbiss, S., Silva-Franco, F., Brunk, B., Foth, B., Hertz-Fowler, C., Berriman, M., & Otto, T. D. (2016). Companion: a web server for annotation and analysis of parasite genomes. Nucleic acids research,44(W1), W29-W34.
dc.relation.referencesSterkers Y, Lachaud L, Bourgeois N, Crobu L, Bastien P, Pagès M (2012). Novel insights into genome plasticity in Eukaryotes: mosaic aneuploidy in Leishmania. Molecular Microbiology, 86: p. 15–23.
dc.relation.referencesSterkers, Y., Crobu, L., Lachaud, L., Pagès, M., & Bastien, P. (2014). Parasexuality and mosaic aneuploidy in Leishmania: Alternative genetics. Trends in Parasitology, 30(9), 429-435. https://doi.org/10.1016/j.pt.2014.07.002
dc.relation.referencesSterkers, Y., Lachaud, L., Crobu, L., Bastien, P., & Pagès, M. (2010). FISH analysis reveals aneuploidy and continual generation of chromosomal mosaicism in Leishmania major. Cellular Microbiology, 13(2), 274-283. https://doi.org/10.1111/j.1462-5822.2010.01534.x
dc.relation.referencesTello, D., Gonzalez‐Garcia, L. N., Gomez, J., Zuluaga‐Monares, J. C., Garcia, R., Angel, R., ... & Duitama, J. (2023). NGSEP 4: Efficient and accurate identification of orthogroups and whole‐genome alignment. Molecular Ecology Resources, 23(3), 712–724.
dc.relation.referencesTorres, D. C., Ribeiro-Alves, M., Romero, G. A. S., Dávila, A. M. R., & Cupolillo, E. (2013). Assessment of drug resistance related genes as candidate markers for treatment outcome prediction of cutaneous leishmaniasis in Brazil. Acta Tropica, 126(2), 132-141. https://doi.org/10.1016/j.actatropica.2013.02.002
dc.relation.referencesUbeda, J. M., Raymond, F., Mukherjee, A., Plourde, M., Gingras, H., Roy, G., Lapointe, A., Leprohon, P., Papadopoulou, B., Corbeil, J., & Ouellette, M. (2014). Genome-wide stochastic adaptive DNA amplification at direct and inverted DNA repeats in the parasite Leishmania. PLoS Biology, 12(5), e1001868. https://doi.org/10.1371/journal.pbio.1001868
dc.relation.referencesUeno, N., & Wilson, M. E. (2012). Receptor-mediated phagocytosis of Leishmania: Implications for intracellular survival. Trends in Parasitology, 28(8), 335–344. https://doi.org/10.1016/j.pt.2012.05.002
dc.relation.referencesUrrea Montes, D. A. (2019). Variación estructural genómica en cepas colombianas de Leishmania (Viannia) panamensis y su relación con virulencia en ratones BALB/c [Tesis doctoral, Universidad de Antioquía].
dc.relation.referencesUrrea, D. A., Duitama, J., Imamura, H., Alzate, J. F., Gil, J., Muñoz, N., Villa, J. A., Dujardin, J. C., Ramírez-Pineda, J. R., & Triana-Chávez, O. (2018). Genomic analysis of Colombian Leishmania panamensis strains with different levels of virulence. Scientific Reports, 8, 17336. https://doi.org/10.1038/s41598-018-35778-6
dc.relation.referencesVan der Luit, A. H., Budde, M., Ruurs, P., Verheij, M., & Van Blitterswijk, W. J. (2002). Alkyllysophospholipid accumulates in lipid rafts and induces apoptosis via raft-dependent endocytosis and inhibition of phosphatidylcholine synthesis. Journal of Biological Chemistry, 277(42), 39541-39547. https://doi.org/10.1074/jbc.M205395200
dc.relation.referencesVanaerschot, M., Decuypere, S., Berg, M., Roy, S., & Dujardin, J. C. (2013). Drug-resistant microorganisms with a higher fitness—Can medicines boost pathogens? Critical Reviews in Microbiology, 39(4), 384–394.
dc.relation.referencesVega, J. C., Sanchez, B. F., Montero, L. M., Montaña, R., Mahecha, M…Reithinger, R. (2007). Short communication: the cost-effectiveness of cutaneous leishmaniasis patient management during an epidemic in Chaparral, Colombia in 2004. Tropical Medicine and International Health, 12(12), 1540–4.
dc.relation.referencesWheeler, R. J., Gull, K., & Gluenz, E. (2012). Detailed interrogation of trypanosome cell biology via differential organelle staining and automated image analysis. BMC Biology, 10, 1.
dc.relation.referencesWu, Y., El Fakhry, Y., Sereno, D., Tamar, S., & Papadopoulou, B. (2000). A new developmentally regulated gene family in Leishmania amastigotes encoding a homolog of amastin surface proteins. Molecular and Biochemical Parasitology, 110(2), 345-357. https://doi.org/10.1016/S0166-6851(00)00285-7
dc.relation.referencesWyllie, S., Cunningham, M. L., & Fairlamb, A. H. (2004). Dual action of antimonial drugs on thiol redox metabolism in the human pathogen Leishmania donovani. The Journal of Biological Chemistry, 17, 279(38), 39925-32. doi: 10.1074/jbc.M405635200.
dc.relation.referencesZauli-Nascimento, R. C., Miguel, D. C., Yokoyama-Yasunaka, J. K. U., Pereira, L. I. A., Pelli de Oliveira, M. A., Ribeiro-Dias, F., Dorta, M. L., & Uliana, S. R. B. (2009). In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B. Tropical Medicine & International Health, 15(1), 68-76. https://doi.org/10.1111/j.1365-3156.2009.02414.x
dc.relation.referencesZhang, H., Yan, R., Liu, Y., Yu, M., He, Z., Xiao, J., et al. (2025). Progress in antileishmanial drugs: Mechanisms, challenges, and prospects. PLoS Neglected Tropical Diseases, 19(1), e0012735. https://doi.org/10.1371/journal.pntd.0012735
dc.relation.referencesZhang, W. W. & Matlashewski, G. (2019). Single-Strand Annealing Plays a Major Role in Double-Strand DNA Break Repair Following CRISPR-Cas9 Cleavage in Leishmania. mSphere, 4(4), e00408–e00419. doi: 10.1128/mSphere.00408-19.
dc.relation.referencesZhang, W. W., & Matlashewski, G. (2015). CRISPR-Cas9-mediated genome editing in Leishmania donovani. mBio, 6(4), e00861. https://doi.org/10.1128/mBio.00861-15
dc.relation.referencesZhao, Y. L., Lu, Z. Y., Zhang, X., Liu, W. W., Yao, G. D., Liu, X. L., ... & Ikejima, T. (2018). Gelatin promotes cell aggregation and pro-inflammatory cytokine production in PMA-stimulated U937 cells by augmenting the endocytosis–autophagy pathway. The International Journal of Biochemistry & Cell Biology, 95, 132–142. https://doi.org/10.1016/j.biocel.2018.01.002
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.licenseReconocimiento 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.ddc570 - Biología::578 - Historia natural de los organismos y temas relacionadosspa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.ddc610 - Medicina y salud::616 - Enfermedadesspa
dc.subject.decsAntibacterianosspa
dc.subject.decsAnti-Bacterial Agentseng
dc.subject.decsTransportadoras de Casetes de Unión a ATPspa
dc.subject.decsATP-Binding Cassette Transporterseng
dc.subject.decsLeishmaniaspa
dc.subject.decsLeishmaniaeng
dc.subject.decsTécnicas In Vitrospa
dc.subject.decsIn Vitro Techniqueseng
dc.subject.proposalLeishmania (Viannia) guyanensisspa
dc.subject.proposalLeishmania (Viannia) braziliensisspa
dc.subject.proposalLeishmaniasis cutáneaspa
dc.subject.proposalToleranciaspa
dc.subject.proposalGlucantimespa
dc.subject.proposalAnfotericina Bspa
dc.subject.proposalMiltefosinaspa
dc.subject.proposalGenómicaspa
dc.subject.proposalToleranceeng
dc.subject.proposalGlucantimeeng
dc.subject.proposalAmphotericin Beng
dc.subject.proposalMiltefosineeng
dc.subject.proposalGenomicseng
dc.subject.unescoGenéticaspa
dc.subject.unescoGeneticseng
dc.titleCaracterización de la respuesta de Leishmania (Viannia) guyanensis a fármacos de utilidad clínica en el tratamiento de leishmaniasis cutánea mediante herramientas de genómica funcionalspa
dc.title.translatedCharacterization of the response of Leishmania (Viannia) guyanensis to clinically relevant drugs used in the treatment of cutaneous leishmaniasis through functional genomics toolseng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdcc
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
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dc.type.driverinfo:eu-repo/semantics/masterThesis
dc.type.redcolhttp://purl.org/redcol/resource_type/TM
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentPúblico generalspa
dcterms.audience.professionaldevelopmentResponsables políticosspa
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oaire.fundernameMinCiencias- Convocatoria 7spa

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