Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada

La leishmaniasis cutánea (LC) es una enfermedad tropical caracterizada por úlceras cutáneas, en ocasiones con lesiones satélites y linfangitis nodular. Los parásitos Leishmania, transmitidos por vectores flebótomos, causan este problema de salud pública generalizado que afecta a millones de personas...

Full description

Autores:
Tipo de recurso:
Fecha de publicación:
2024
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
spa
OAI Identifier:
oai:repository.urosario.edu.co:10336/43490
Acceso en línea:
https://repository.urosario.edu.co/handle/10336/43490
Palabra clave:
Microbioma
Microbiota
Procariotas
Eucariotas
Piel
Leishmaniasis Cutánea
Microbiome
Microbiota
Prokaryotes
Eukaryotes
Skin
Cutaneous Leishmaniasis
Rights
License
Attribution-NonCommercial-NoDerivatives 4.0 International
id EDOCUR2_56f8c6085d7efc8fb15871edf0ef6943
oai_identifier_str oai:repository.urosario.edu.co:10336/43490
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.none.fl_str_mv Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
dc.title.TranslatedTitle.none.fl_str_mv Prokaryotic and eukaryotic skin microbiota modifications triggered by Leishmania infection in localized Cutaneous Leishmaniasis
title Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
spellingShingle Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
Microbioma
Microbiota
Procariotas
Eucariotas
Piel
Leishmaniasis Cutánea
Microbiome
Microbiota
Prokaryotes
Eukaryotes
Skin
Cutaneous Leishmaniasis
title_short Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
title_full Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
title_fullStr Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
title_full_unstemmed Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
title_sort Modificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizada
dc.contributor.advisor.none.fl_str_mv Ramírez González, Juan David
Patiño Blanco, Luz Helena
dc.contributor.gruplac.none.fl_str_mv Grupo de Investigaciones Microbiológicas UR (GIMUR)
dc.subject.none.fl_str_mv Microbioma
Microbiota
Procariotas
Eucariotas
Piel
Leishmaniasis Cutánea
topic Microbioma
Microbiota
Procariotas
Eucariotas
Piel
Leishmaniasis Cutánea
Microbiome
Microbiota
Prokaryotes
Eukaryotes
Skin
Cutaneous Leishmaniasis
dc.subject.keyword.none.fl_str_mv Microbiome
Microbiota
Prokaryotes
Eukaryotes
Skin
Cutaneous Leishmaniasis
description La leishmaniasis cutánea (LC) es una enfermedad tropical caracterizada por úlceras cutáneas, en ocasiones con lesiones satélites y linfangitis nodular. Los parásitos Leishmania, transmitidos por vectores flebótomos, causan este problema de salud pública generalizado que afecta a millones de personas en todo el mundo. La complejidad de CL proviene de diversas especies de Leishmania y de complejas interacciones con el huésped. Por lo tanto, este estudio tiene como objetivo arrojar luz sobre la distribución espacio-temporal de las especies de Leishmania y explorar la influencia de la microbiota cutánea en la progresión de la enfermedad. Analizamos 40 muestras de pacientes con CL en tres bases militares en Colombia. Utilizando la secuenciación de la proteína de choque térmico 70 de Oxford Nanopore, identificamos especies de Leishmania y perfilamos la microbiota en lesiones de CL y las correspondientes extremidades sanas. La secuenciación de Illumina de los genes 16S-rRNA y 18S-rRNA ayudó a analizar las comunidades procarióticas y eucariotas. Nuestra investigación descubrió una superposición espacio-temporal entre regiones de alta incidencia de CL y nuestras ubicaciones de muestreo, lo que indica la coexistencia de varias especies de Leishmania. L. naiffi surgió como un descubrimiento digno de mención. Además, nuestro estudio profundizó en los cambios en la microbiota cutánea asociados con las lesiones de CL obtenidas mediante raspado en comparación con la piel sana obtenida mediante cepillado de las extremidades superiores e inferiores. Observamos alteraciones en la diversidad microbiana, tanto en comunidades procarióticas como eucariotas, dentro de las áreas lesionadas, lo que significa el papel potencial de la microbiota en la patogénesis de la CL. El aumento significativo de familias bacterianas específicas, como Staphylococcaceae y Streptococcaceae, dentro de las lesiones de CL indica su contribución a la inflamación local. En esencia, nuestro estudio contribuye a la investigación en curso sobre la CL, destacando la necesidad de un enfoque multifacético para descifrar las intrincadas interacciones entre la leishmaniasis y la microbiota cutánea.
publishDate 2024
dc.date.accessioned.none.fl_str_mv 2024-10-04T12:45:22Z
dc.date.available.none.fl_str_mv 2024-10-04T12:45:22Z
dc.date.created.none.fl_str_mv 2024-03-13
dc.type.none.fl_str_mv bachelorThesis
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.document.none.fl_str_mv Artículo
dc.type.spa.none.fl_str_mv Artículo
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/43490
url https://repository.urosario.edu.co/handle/10336/43490
dc.language.iso.none.fl_str_mv spa
language spa
dc.relation.uri.none.fl_str_mv https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012029
dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.none.fl_str_mv Abierto (Texto Completo)
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
Abierto (Texto Completo)
http://creativecommons.org/licenses/by-nc-nd/4.0/
http://purl.org/coar/access_right/c_abf2
dc.format.extent.none.fl_str_mv 53 pp
dc.format.mimetype.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidad del Rosario
dc.publisher.department.none.fl_str_mv Facultad de Ciencias Naturales
dc.publisher.gcio.none.fl_str_mv Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR)
Grupo de Investigación en Enfermedades Tropicales del Ejército (GINETEJ)
dc.publisher.program.none.fl_str_mv Maestría en Ciencias Naturales
publisher.none.fl_str_mv Universidad del Rosario
institution Universidad del Rosario
dc.source.bibliographicCitation.none.fl_str_mv Ruiz-Postigo JA, Jain S, Mikhailov A, Maia-Elkhoury AN, Valadas S, Warusavithana S, et al. Global leishmaniasis surveillance: 2019–2020, a baseline for the 2030 roadmap. 3 Sep 2021. [cited 22 Sep 2023]. Available: https://www.who.int/publications-detail-redirect/who-wer9635-401-419
Correa-Cárdenas CA, Pérez J, Patino LH, Ramírez JD, Duque MC, Romero Y, et al. Distribution, treatment outcome and genetic diversity of Leishmania species in military personnel from Colombia with cutaneous leishmaniasis. BMC Infectious Diseases. 2020;20: 938. doi: 10.1186/s12879-020-05529-y
Patino LH, Mendez C, Rodriguez O, Romero Y, Velandia D, Alvarado M, et al. Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army. PLOS Neglected Tropical Diseases. 2017;11: e0005876. doi: 10.1371/journal.pntd.0005876
Herrera G, Teherán A, Pradilla I, Vera M, Ramírez JD. Geospatial-temporal distribution of Tegumentary Leishmaniasis in Colombia (2007–2016). PLOS Neglected Tropical Diseases. 2018;12: e0006419. doi: 10.1371/journal.pntd.0006419
Herrera G, Barragán N, Luna N, Martínez D, De Martino F, Medina J, et al. An interactive database of Leishmania species distribution in the Americas. Sci Data. 2020;7: 110. doi: 10.1038/s41597-020-0451-5
Ovalle-Bracho C, Londoño-Barbosa D, Salgado-Almario J, González C. Evaluating the spatial distribution of Leishmania parasites in Colombia from clinical samples and human isolates (1999 to 2016). PLoS One. 2019;14. doi: 10.1371/journal.pone.0214124
INS IN de S. LEISHMANIASIS CUTÁNEA, MUCOSA Y VISCERAL. COLOMBIA 2018. 2018. Available: https://www.ins.gov.co/buscador-eventos/Informesdeevento/LEISHMANIASIS_2018.pdf
Tatu A, Radaschin D. A short review about cutaneous microbiome. 2018;41: 237–241. doi: 10.35219/ann-ugal-math-phys-mec.2018.2.17
Baldwin HE, Bhatia ND, Friedman A, Eng RM, Seite S. The Role of Cutaneous Microbiota Harmony in Maintaining a Functional Skin Barrier. J Drugs Dermatol. 2017;16: 12–18.
Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16: 143–155. doi: 10.1038/nrmicro.2017.157
De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms. 2021;9. doi: 10.3390/microorganisms9020353
Ederveen THA, Smits JPH, Boekhorst J, Schalkwijk J, van den Bogaard EH, Zeeuwen PLJM. Skin microbiota in health and disease: From sequencing to biology. J Dermatol. 2020;47: 1110–1118. doi: 10.1111/1346-8138.15536
Flowers L, Grice EA. The Skin Microbiota: Balancing Risk and Reward. Cell Host Microbe. 2020;28: 190–200. doi: 10.1016/j.chom.2020.06.017
Loomis KH, Wu SK, Ernlund A, Zudock K, Reno A, Blount K, et al. A mixed community of skin microbiome representatives influences cutaneous processes more than individual members. Microbiome. 2021;9: 22. doi: 10.1186/s40168-020-00963-1
Assarsson M, Duvetorp A, Dienus O, Söderman J, Seifert O. Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B. Acta Derm Venereol. 2018;98: 428–436. doi: 10.2340/00015555-2859
Baviera G, Leoni MC, Capra L, Cipriani F, Longo G, Maiello N, et al. Microbiota in Healthy Skin and in Atopic Eczema. Biomed Res Int. 2014;2014: 436921. doi: 10.1155/2014/436921
Bjerre RD, Bandier J, Skov L, Engstrand L, Johansen JD. The role of the skin microbiome in atopic dermatitis: a systematic review. British Journal of Dermatology. 2017;177: 1272–1278. doi: 10.1111/bjd.15390
Chen L, Li J, Zhu W, Kuang Y, Liu T, Zhang W, et al. Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies. Front Microbiol. 2020;11: 589726. doi: 10.3389/fmicb.2020.589726
Fyhrquist N, Muirhead G, Prast-Nielsen S, Jeanmougin M, Olah P, Skoog T, et al. Microbe-host interplay in atopic dermatitis and psoriasis. Nat Commun. 2019;10: 4703. doi: 10.1038/s41467-019-12253-y
Picardo M, Ottaviani M. Skin microbiome and skin disease: the example of rosacea. J Clin Gastroenterol. 2014;48 Suppl 1: S85–86. doi: 10.1097/MCG.0000000000000241
Ring HC, Thorsen J, Saunte DM, Lilje B, Bay L, Riis PT, et al. The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls. JAMA Dermatol. 2017;153: 897–905. doi: 10.1001/jamadermatol.2017.0904
Oliveira MR de, Tafuri WL, Nicoli JR, Vieira EC, Melo MN, Vieira LQ. Influence of microbiota in experimental cutaneous leishmaniasis in swiss MICE. Rev Inst Med trop S Paulo. 1999;41: 87–94. doi: 10.1590/s0036-46651999000200005
Ec V, Jr N, T M-S, Me S, Ca da C, W M, et al. Cutaneous leishmaniasis in germfree, gnotobiotic, and conventional mice. Revista do Instituto de Medicina Tropical de Sao Paulo. 1987;29. doi: 10.1590/s0036-46651987000600009
Gimblet C, Meisel JS, Loesche MA, Cole SD, Horwinski J, Novais FO, et al. Cutaneous leishmaniasis induces a transmissible dysbiotic skin microbiota that promotes skin inflammation. Cell Host Microbe. 2017;22: 13–24.e4. doi: 10.1016/j.chom.2017.06.006
Salgado VR, Queiroz ATL de, Sanabani SS, Oliveira CI de, Carvalho EM, Costa JML, et al. The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin. Mem Inst Oswaldo Cruz. 2016;111: 241–251. doi: 10.1590/0074-02760150436
Ereqat S, Al-Jawabreh A, Abdeen Z, Al-Jawabreh H, Nasereddin A. Characterization of Leishmania Ulcers Microbiota Using Next-Generation Sequencing. Al-Quds Acad Res. 2021. doi: 10.47874/2021p8
Jayasena Kaluarachchi TD, Campbell PM, Wickremasinghe R, Ranasinghe S, Wickremasinghe R, Yasawardene S, et al. Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds. Sci Rep. 2021;11: 23181. doi: 10.1038/s41598-021-02388-8
Amorim CF, Lovins VM, Singh TP, Novais FO, Harris JC, Lago AS, et al. Multi-omic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity. medRxiv; 2023. p. 2023.02.02. doi: 10.1101/2023.02.02.23285247
Beiter KJ, Wentlent ZJ, Hamouda AR, Thomas BN. Nonconventional opponents: a review of malaria and leishmaniasis among United States Armed Forces. PeerJ. 2019;7: e6313. doi: 10.7717/peerj.6313
Hernández AM, Gutierrez JD, Xiao Y, Branscum AJ, Cuadros DF. Spatial epidemiology of cutaneous leishmaniasis in Colombia: socioeconomic and demographic factors associated with a growing epidemic. Transactions of The Royal Society of Tropical Medicine and Hygiene. 2019;113: 560–568. doi: 10.1093/trstmh/trz043
Requena JM, Chicharro C, García L, Parrado R, Puerta CJ, Cañavate C. Sequence analysis of the 3’-untranslated region of HSP70 (type I) genes in the genus Leishmania: its usefulness as a molecular marker for species identification. Parasites & Vectors. 2012;5: 87. doi: 10.1186/1756-3305-5-87
Ramírez CA, Requena JM, Puerta CJ. Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus: genomic organization and UTRs characterization. Parasites & Vectors. 2011;4: 166. doi: 10.1186/1756-3305-4-166
Hernández C, Alvarez C, González C, Ayala MS, León CM, Ramírez JD. Identification of six New World Leishmania species through the implementation of a High-Resolution Melting (HRM) genotyping assay. Parasit Vectors. 2014;7: 501. doi: 10.1186/s13071-014-0501-y
Fraga J, Montalvo AM, De Doncker S, Dujardin J-C, Van der Auwera G. Phylogeny of Leishmania species based on the heat-shock protein 70 gene. Infect Genet Evol. 2010;10: 238–245. doi: 10.1016/j.meegid.2009.11.007
Akhoundi M, Kuhls K, Cannet A, Votýpka J, Marty P, Delaunay P, et al. A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies. PLoS Negl Trop Dis. 2016;10: e0004349. doi: 10.1371/journal.pntd.0004349
WMA—The World Medical Association-Declaración de Helsinki de la AMM–Principios éticos para las investigaciones médicas en seres humanos. [cited 22 Sep 2023]. Available: https://www.wma.net/es/policies-post/declaracion-de-helsinki-de-la-amm-principios-eticos-para-las-investigaciones-medicas-en-seres-humanos/
INS IN de S. Protocolo de Vigilancia de Leishmaniasis. INS; 2022. Available: https://www.ins.gov.co/buscador-eventos/Lineamientos/PRO_Leishmaniasis.pdf
OPS OP de la S. Manual de procedimientos para vigilancia y control de las leishmaniasis en las Américas. 1st ed. Washington, D.C.: OPS; 2019. Available: 10.37774/9789275320631
Klymiuk I, Bambach I, Patra V, Trajanoski S, Wolf P. 16S Based Microbiome Analysis from Healthy Subjects’ Skin Swabs Stored for Different Storage Periods Reveal Phylum to Genus Level Changes. Front Microbiol. 2016;7: 2012. doi: 10.3389/fmicb.2016.02012
Novogene. 16S/18S/ITS Amplicon Metagenomic Sequencing. In: Novogene [Internet]. [cited 26 Oct 2021]. Available: https://en.novogene.com/16s-18s-its-amplicon-metagenomic-sequencing/
Ramírez JD, Cao L, Castillo-Castañeda AC, Patino LH, Ayala MS, Cordon-Cardo C, et al. Clinical performance of a quantitative pan-genus Leishmania Real-time PCR assay for diagnosis of cutaneous and visceral leishmaniasis. Practical Laboratory Medicine. 2023;37: e00341. doi: 10.1016/j.plabm.2023.e00341
Patiño LH, Castillo-Castañeda A, Muñoz M, Jaimes J, Luna N, Hernández C, et al. Development of an amplicon-based Next Generation Sequencing protocol to identify Leishmania species and other trypanosomatids in Leishmaniasis endemic areas. Microbiol Spectr. 2021;(article accepted for publication). doi: 10.1128/Spectrum.00652-21
Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, et al. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486: 207–214. doi: 10.1038/nature11234
Vega L, Herrera G, Muñoz M, Patarroyo MA, Maloney JG, Santín M, et al. Gut microbiota profiles in diarrheic patients with co-occurrence of Clostridioides difficile and Blastocystis. PLOS ONE. 2021;16: e0248185. doi: 10.1371/journal.pone.0248185
Herrera G, Vega L, Patarroyo MA, Ramírez JD, Muñoz M. Gut microbiota composition in health-care facility-and community-onset diarrheic patients with Clostridioides difficile infection. Sci Rep. 2021;11: 10849. doi: 10.1038/s41598-021-90380-7
Andrews S. Babraham Bioinformatics—FastQC A Quality Control tool for High Throughput Sequence Data. [cited 26 Oct 2021]. Available: https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Ewels P, Magnusson M, Lundin S, Käller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32: 3047–3048. doi: 10.1093/bioinformatics/btw354
Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37: 852–857. doi: 10.1038/s41587-019-0209-9
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13: 581–583. doi: 10.1038/nmeth.3869
Sfriso R, Egert M, Gempeler M, Voegeli R, Campiche R. Revealing the secret life of skin—with the microbiome you never walk alone. International Journal of Cosmetic Science. 2020;42: 116–126. doi: 10.1111/ics.12594
Boxberger M, Cenizo V, Cassir N, La Scola B. Challenges in exploring and manipulating the human skin microbiome. Microbiome. 2021;9: 125. doi: 10.1186/s40168-021-01062-5
Carmona-Cruz S, Orozco-Covarrubias L, Sáez-de-Ocariz M. The Human Skin Microbiome in Selected Cutaneous Diseases. Frontiers in Cellular and Infection Microbiology. 2022;12. Available: https://www.frontiersin.org/articles/10.3389/fcimb.2022.834135
Patiño LH, Castillo-Castañeda AC, Muñoz M, Jaimes JE, Luna-Niño N, Hernández C, et al. Development of an Amplicon-Based Next-Generation Sequencing Protocol to Identify Leishmania Species and Other Trypanosomatids in Leishmaniasis Endemic Areas. Microbiol Spectr. 2021; e0065221. doi: 10.1128/Spectrum.00652-21
Castillo-Castañeda A, Patiño LH, Muñoz M, Ayala MS, Segura M, Bautista J, et al. Amplicon-based next-generation sequencing reveals the co-existence of multiple Leishmania species in patients with visceral leishmaniasis. Int J Infect Dis. 2022;115: 35–38. doi: 10.1016/j.ijid.2021.11.029
Cantanhêde LM, Cupolillo E. Leishmania (Viannia) naiffi Lainson & Shaw 1989. Parasit Vectors. 2023;16: 194. doi: 10.1186/s13071-023-05814-0
Pratlong F, Deniau M, Darie H, Eichenlaub S, Pröll S, Garrabe E, et al. Human cutaneous leishmaniasis caused by Leishmania naiffi is wide-spread in South America. Ann Trop Med Parasitol. 2002;96: 781–785. doi: 10.1179/000349802125002293
van der Snoek EM, Lammers AM, Kortbeek LM, Roelfsema JH, Bart A, Jaspers C a JJ. Spontaneous cure of American cutaneous leishmaniasis due to Leishmania naiffi in two Dutch infantry soldiers. Clin Exp Dermatol. 2009;34: e889–891. doi: 10.1111/j.1365-2230.2009.03658.x
Alexandre J, Sadlova J, Lestinova T, Vojtkova B, Jancarova M, Podesvova L, et al. Experimental infections and co-infections with Leishmania braziliensis and Leishmania infantum in two sand fly species, Lutzomyia migonei and Lutzomyia longipalpis. Sci Rep. 2020;10: 3566. doi: 10.1038/s41598-020-60600-7
Se G, Sl H, K H, Ja S, Ea G. The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes. 2013;62. doi: 10.2337/db12-0771
Mudrik-Zohar H, Carasso S, Gefen T, Zalmanovich A, Katzir M, Cohen Y, et al. Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods. Frontiers in Cellular and Infection Microbiology. 2022;12. Available: https://www.frontiersin.org/articles/10.3389/fcimb.2022.836699
Hershko AY. Insights into the mast cell-microbiome connection in the skin. J Allergy Clin Immunol. 2017;139: 1137–1139. doi: 10.1016/j.jaci.2016.11.016
Camanocha A, Dewhirst FE. Host-associated bacterial taxa from Chlorobi, Chloroflexi, GN02, Synergistetes, SR1, TM7, and WPS-2 Phyla/candidate divisions. J Oral Microbiol. 2014;6. doi: 10.3402/jom.v6.25468
Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner ACR, Yu W-H, et al. The human oral microbiome. J Bacteriol. 2010;192: 5002–5017. doi: 10.1128/JB.00542-10
Sedghi L, DiMassa V, Harrington A, Lynch SV, Kapila YL. The oral microbiome: Role of key organisms and complex networks in oral health and disease. Periodontology 2000. 2021;87: 107. doi: 10.1111/prd.12393
Irfan M, Delgado RZR, Frias-Lopez J. The Oral Microbiome and Cancer. Frontiers in Immunology. 2020;11. doi: 10.3389/fimmu.2020.591088
Misra P, Singh S. Site specific microbiome of Leishmania parasite and its cross-talk with immune milieu. Immunol Lett. 2019;216: 79–88. doi: 10.1016/j.imlet.2019.10.004
A P, Rw J, M O, Lv C, P S, G N, et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. The Journal of experimental medicine. 2001;193. doi: 10.1084/jem.193.9.1067
Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Götz F. Inactivation of the dlt Operon inStaphylococcus aureus Confers Sensitivity to Defensins, Protegrins, and Other Antimicrobial Peptides*. Journal of Biological Chemistry. 1999;274: 8405–8410. doi: 10.1074/jbc.274.13.8405
Charmoy M, Hurrell BP, Romano A, Lee SH, Ribeiro-Gomes F, Riteau N, et al. The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice. European Journal of Immunology. 2016;46: 897–911. doi: 10.1002/eji.201546015
Singh TP, Carvalho AM, Sacramento LA, Grice EA, Scott P. Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis. PLOS Pathogens. 2021;17: e1009693. doi: 10.1371/journal.ppat.1009693
Shalon D, Culver RN, Grembi JA, Folz J, Treit PV, Shi H, et al. Profiling the human intestinal environment under physiological conditions. Nature. 2023;617: 581–591. doi: 10.1038/s41586-023-05989-
Meisel JS, Sfyroera G, Bartow-McKenney C, Gimblet C, Bugayev J, Horwinski J, et al. Commensal microbiota modulate gene expression in the skin. Microbiome. 2018;6: 20. doi: 10.1186/s40168-018-0404-9
Naik S, Bouladoux N, Linehan JL, Han S-J, Harrison OJ, Wilhelm C, et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature. 2015;520: 104–108. doi: 10.1038/nature14052
Liu C, Ponsero AJ, Armstrong DG, Lipsky BA, Hurwitz BL. The dynamic wound microbiome. BMC Medicine. 2020;18: 358. doi: 10.1186/s12916-020-01820-6
Verbanic S, Shen Y, Lee J, Deacon JM, Chen IA. Microbial predictors of healing and short-term effect of debridement on the microbiome of chronic wounds. npj Biofilms Microbiomes. 2020;6: 1–11. doi: 10.1038/s41522-020-0130-5
Isaac-Márquez AP, Lezama-Dávila CM. Detection of pathogenic bacteria in skin lesions of patients with chiclero’s ulcer: reluctant response to antimonial treatment. Mem Inst Oswaldo Cruz. 2003;98: 1093–1095. doi: 10.1590/S0074-02762003000800021
Fontes CO, Carvalho MAR, Nicoli JR, Hamdan JS, Mayrink W, Genaro O, et al. Identification and antimicrobial susceptibility of micro-organisms recovered from cutaneous lesions of human American tegumentary leishmaniasis in Minas Gerais, Brazil. J Med Microbiol. 2005;54: 1071–1076. doi: 10.1099/jmm.0.46070-0
Antonio L de F, Lyra MR, Saheki MN, Schubach A de O, Miranda L de FC, Madeira M de F, et al. Effect of secondary infection on epithelialisation and total healing of cutaneous leishmaniasis lesions. Mem Inst Oswaldo Cruz. 2017;112: 640–646. doi: 10.1590/0074-02760160557
Layegh P, Ghazvini K, Moghiman T, Hadian F, Zabolinejad N, Pezeshkpour F. Bacterial Contamination in Cutaneous Leishmaniasis: Its Effect on the Lesions’ Healing Course. Indian J Dermatol. 2015;60: 211. doi: 10.4103/0019-5154.152560
Bk P, Kh P, Ry H, Cn L, Sm M. The Gut-Skin Microbiota Axis and Its Role in Diabetic Wound Healing-A Review Based on Current Literature. International journal of molecular sciences. 2022;23. doi: 10.3390/ijms23042375
Olejniczak-Staruch I, Ciążyńska M, Sobolewska-Sztychny D, Narbutt J, Skibińska M, Lesiak A. Alterations of the Skin and Gut Microbiome in Psoriasis and Psoriatic Arthritis. Int J Mol Sci. 2021;22: 3998. doi: 10.3390/ijms22083998
A O. [Corynebacterium-associated skin infections]. Annales de dermatologie et de venereologie. 2018;145. doi: 10.1016/j.annder.2018.01.039
Dréno B, Dagnelie MA, Khammari A, Corvec S. The Skin Microbiome: A New Actor in Inflammatory Acne. Am J Clin Dermatol. 2020;21: 18–24. doi: 10.1007/s40257-020-00531-1
Guerrero DM, Perez F, Conger NG, Solomkin JS, Adams MD, Rather PN, et al. Acinetobacter baumannii-Associated Skin and Soft Tissue Infections: Recognizing a Broadening Spectrum of Disease*. Surg Infect (Larchmt). 2010;11: 49–57. doi: 10.1089/sur.2009.022
Reina R, León-Moya C, Garnacho-Montero J. Treatment of Acinetobacter baumannii severe infections. Med Intensiva (Engl Ed). 2022;46: 700–710. doi: 10.1016/j.medine.2022.08.007
Zhang J, Zheng Y-C, Chu Y-L, Cui X-M, Wei R, Bian C, et al. Skin infectome of patients with a tick bite history. Front Cell Infect Microbiol. 2023;13: 1113992. doi: 10.3389/fcimb.2023.1113992
Willmott T, Campbell PM, Griffiths CEM, O’Connor C, Bell M, Watson REB, et al. Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity. Front Aging. 2023;4: 1217635. doi: 10.3389/fragi.2023.1217635
H E, Hb T, Mwj S, B B, Ri T, Sr K, et al. Depletion of Saccharomyces cerevisiae in psoriasis patients, restored by Dimethylfumarate therapy (DMF). PloS one. 2017;12. doi: 10.1371/journal.pone.0176955
S H, C P, J B, S R, Z K, A M, et al. Saccharomyces cerevisiae as a skin physiology, pathology, and treatment model. Dermatology online journal. 2020;26. Available: https://pubmed.ncbi.nlm.nih.gov/33342171/
Díaz MGU, Uzcátegui AM, Sáenz AM, Solano M. Microbiota, microbioma y su manipulación en enfermedades de la piel. Dermatología Venezolana. 2020;58. Available: https://revista.svderma.org/index.php/ojs/article/view/1468
Rincón S, Celis A, Sopó L, Motta A, García MCC de. Malassezia yeast species isolated from patients with dermatologic lesions. Biomédica. 2005;25: 189–95. doi: 10.7705/biomedica.v25i2.1341
Lind AL, Pollard KS. Accurate and sensitive detection of microbial eukaryotes from whole metagenome shotgun sequencing. Microbiome. 2021;9: 58. doi: 10.1186/s40168-021-01015-y
Celis AM, García MCC de. Genetic polymorphism of Malassezia spp. yeast isolates from individuals with and without dermatological lesions. Biomédica. 2005;25: 481–7. doi: 10.7705/biomedica.v25i4.1374
Sommer B, Overy DP, Kerr RG. Identification and characterization of lipases from Malassezia restricta, a causative agent of dandruff. FEMS Yeast Research. 2015;15: fov078. doi: 10.1093/femsyr/fov078
Hadrich I, Khemakhem N, Ilahi A, Trabelsi H, Sellami H, Makni F, et al. Genotypic Analysis of the Population Structure in Malassezia globosa and Malassezia restricta. J Fungi (Basel). 2023;9: 263. doi: 10.3390/jof9020263
Green BJ. Emerging Insights into the Occupational Mycobiome. Curr Allergy Asthma Rep. 2018;18: 62. doi: 10.1007/s11882-018-0818-2
D L, O A, Ce E. Approach to chronic wound infections. The British journal of dermatology. 2015;173. doi: 10.1111/bjd.13677
Gardiner M, Vicaretti M, Sparks J, Bansal S, Bush S, Liu M, et al. A longitudinal study of the diabetic skin and wound microbiome. PeerJ. 2017;5: e3543. doi: 10.7717/peerj.3543
Dowd SE, Sun Y, Secor PR, Rhoads DD, Wolcott BM, James GA, et al. Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC Microbiol. 2008;8: 43. doi: 10.1186/1471-2180-8-43
Rd W, Jd H, Ej R, Ld K, Cd P, Ra W, et al. Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2016;24. doi: 10.1111/wrr.12370
M L, Se G, L K, J H, Q Z, Bp H, et al. Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing. The Journal of investigative dermatology. 2017;137. doi: 10.1016/j.jid.2016.08.009
Kalan LR, Meisel JS, Loesche MA, Horwinski J, Soaita I, Chen X, et al. Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy. Cell Host Microbe. 2019;25: 641–655.e5. doi: 10.1016/j.chom.2019.03.006
Rahim K, Saleha S, Zhu X, Huo L, Basit A, Franco OL. Bacterial Contribution in Chronicity of Wounds. Microb Ecol. 2017;73: 710–721. doi: 10.1007/s00248-016-0867-9
Jneid J, Cassir N, Schuldiner S, Jourdan N, Sotto A, Lavigne J-P, et al. Exploring the Microbiota of Diabetic Foot Infections With Culturomics. Front Cell Infect Microbiol. 2018;8: 282. doi: 10.3389/fcimb.2018.00282
Ammons MCB, Morrissey K, Tripet BP, Van Leuven JT, Han A, Lazarus GS, et al. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds. PLoS One. 2015;10: e0126735. doi: 10.1371/journal.pone.0126735
dc.source.instname.none.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.none.fl_str_mv reponame:Repositorio Institucional EdocUR
bitstream.url.fl_str_mv https://repository.urosario.edu.co/bitstreams/f9b4922b-74db-4db1-b03d-c745992e4fc2/download
https://repository.urosario.edu.co/bitstreams/82469cfd-c0bc-4ae4-88e0-b19d44941a4c/download
https://repository.urosario.edu.co/bitstreams/1654a095-71a1-4246-b01f-356a8ae85aa3/download
https://repository.urosario.edu.co/bitstreams/36496856-330b-4700-909e-b71dc4116852/download
https://repository.urosario.edu.co/bitstreams/08bd3e0e-ceb9-40e5-81c1-b264aa77ee90/download
https://repository.urosario.edu.co/bitstreams/8bf2e89f-3e08-43c3-9e23-f5a234069863/download
bitstream.checksum.fl_str_mv b2825df9f458e9d5d96ee8b7cd74fde6
3b6ce8e9e36c89875e8cf39962fe8920
e22128b5e5c3330aefd59010ab2c3c70
5791b9e6ca95c4e9c7ac1a4a43864170
e6407e96e73400b9bdc36142681c9a31
ca7c46d644ef1bad9754f9a89ee31d7a
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio institucional EdocUR
repository.mail.fl_str_mv edocur@urosario.edu.co
_version_ 1818106955381604352
spelling Ramírez González, Juan David1011716118600Patiño Blanco, Luz Helena93881362-13b3-40f2-8ae5-45b0f08244b1-1Grupo de Investigaciones Microbiológicas UR (GIMUR)Jaimes Silva, Jesús EduardoHerrera, GiovannyCruz, ClaudiaPérez, JulieCorrea-Cárdenas, Camilo A.Muñoz, MarinaMagíster en Ciencias NaturalesMaestríaPart timed9bcb4f2-18e6-4ca5-8ec8-c1e32226ae8f07f5f951-ff31-4b0f-94f0-7492d0a86f05-16be368c8-6480-4e8c-862f-1c2c96c5cd43-130205fba-7f17-462a-be93-67444efe9c1f-1e48fbab8-25f4-4403-bec6-26cf9232abba-1453006a5-2ec3-4faf-8e32-a9d7075d519d-12024-10-04T12:45:22Z2024-10-04T12:45:22Z2024-03-13La leishmaniasis cutánea (LC) es una enfermedad tropical caracterizada por úlceras cutáneas, en ocasiones con lesiones satélites y linfangitis nodular. Los parásitos Leishmania, transmitidos por vectores flebótomos, causan este problema de salud pública generalizado que afecta a millones de personas en todo el mundo. La complejidad de CL proviene de diversas especies de Leishmania y de complejas interacciones con el huésped. Por lo tanto, este estudio tiene como objetivo arrojar luz sobre la distribución espacio-temporal de las especies de Leishmania y explorar la influencia de la microbiota cutánea en la progresión de la enfermedad. Analizamos 40 muestras de pacientes con CL en tres bases militares en Colombia. Utilizando la secuenciación de la proteína de choque térmico 70 de Oxford Nanopore, identificamos especies de Leishmania y perfilamos la microbiota en lesiones de CL y las correspondientes extremidades sanas. La secuenciación de Illumina de los genes 16S-rRNA y 18S-rRNA ayudó a analizar las comunidades procarióticas y eucariotas. Nuestra investigación descubrió una superposición espacio-temporal entre regiones de alta incidencia de CL y nuestras ubicaciones de muestreo, lo que indica la coexistencia de varias especies de Leishmania. L. naiffi surgió como un descubrimiento digno de mención. Además, nuestro estudio profundizó en los cambios en la microbiota cutánea asociados con las lesiones de CL obtenidas mediante raspado en comparación con la piel sana obtenida mediante cepillado de las extremidades superiores e inferiores. Observamos alteraciones en la diversidad microbiana, tanto en comunidades procarióticas como eucariotas, dentro de las áreas lesionadas, lo que significa el papel potencial de la microbiota en la patogénesis de la CL. El aumento significativo de familias bacterianas específicas, como Staphylococcaceae y Streptococcaceae, dentro de las lesiones de CL indica su contribución a la inflamación local. En esencia, nuestro estudio contribuye a la investigación en curso sobre la CL, destacando la necesidad de un enfoque multifacético para descifrar las intrincadas interacciones entre la leishmaniasis y la microbiota cutánea.Cutaneous Leishmaniasis (CL) is a tropical disease characterized by cutaneous ulcers, sometimes with satellite lesions and nodular lymphangitis. Leishmania parasites, transmitted by sandfly vectors, cause this widespread public health challenge affecting millions worldwide. CL’s complexity stems from diverse Leishmania species and intricate host interactions. Therefore, this study aims to shed light on the spatial-temporal distribution of Leishmania species and exploring the influence of skin microbiota on disease progression. We analyzed 40 samples from CL patients at three military bases across Colombia. Using Oxford Nanopore’s Heat Shock Protein 70 sequencing, we identified Leishmania species and profiled microbiota in CL lesions and corresponding healthy limbs. Illumina sequencing of 16S-rRNA and 18S-rRNA genes helped analyze prokaryotic and eukaryotic communities. Our research uncovered a spatial-temporal overlap between regions of high CL incidence and our sampling locations, indicating the coexistence of various Leishmania species. L. naiffi emerged as a noteworthy discovery. In addition, our study delved into the changes in skin microbiota associated with CL lesions sampled by scraping compared with healthy skin sampled by brushing of upper and lower limbs. We observed alterations in microbial diversity, both in prokaryotic and eukaryotic communities, within the lesioned areas, signifying the potential role of microbiota in CL pathogenesis. The significant increase in specific bacterial families, such as Staphylococcaceae and Streptococcaceae, within CL lesions indicates their contribution to local inflammation. In essence, our study contributes to the ongoing research into CL, highlighting the need for a multifaceted approach to decipher the intricate interactions between Leishmaniasis and the skin microbiota.Universidad del RosarioCentro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR)Grupo de Investigación en Enfermedades Tropicales del Ejército (GINETEJ)53 ppapplication/pdfhttps://repository.urosario.edu.co/handle/10336/43490spaUniversidad del RosarioFacultad de Ciencias NaturalesCentro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR)Grupo de Investigación en Enfermedades Tropicales del Ejército (GINETEJ)Maestría en Ciencias Naturaleshttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012029Attribution-NonCommercial-NoDerivatives 4.0 InternationalAbierto (Texto Completo)http://creativecommons.org/licenses/by-nc-nd/4.0/http://purl.org/coar/access_right/c_abf2Ruiz-Postigo JA, Jain S, Mikhailov A, Maia-Elkhoury AN, Valadas S, Warusavithana S, et al. Global leishmaniasis surveillance: 2019–2020, a baseline for the 2030 roadmap. 3 Sep 2021. [cited 22 Sep 2023]. Available: https://www.who.int/publications-detail-redirect/who-wer9635-401-419Correa-Cárdenas CA, Pérez J, Patino LH, Ramírez JD, Duque MC, Romero Y, et al. Distribution, treatment outcome and genetic diversity of Leishmania species in military personnel from Colombia with cutaneous leishmaniasis. BMC Infectious Diseases. 2020;20: 938. doi: 10.1186/s12879-020-05529-yPatino LH, Mendez C, Rodriguez O, Romero Y, Velandia D, Alvarado M, et al. Spatial distribution, Leishmania species and clinical traits of Cutaneous Leishmaniasis cases in the Colombian army. PLOS Neglected Tropical Diseases. 2017;11: e0005876. doi: 10.1371/journal.pntd.0005876Herrera G, Teherán A, Pradilla I, Vera M, Ramírez JD. Geospatial-temporal distribution of Tegumentary Leishmaniasis in Colombia (2007–2016). PLOS Neglected Tropical Diseases. 2018;12: e0006419. doi: 10.1371/journal.pntd.0006419Herrera G, Barragán N, Luna N, Martínez D, De Martino F, Medina J, et al. An interactive database of Leishmania species distribution in the Americas. Sci Data. 2020;7: 110. doi: 10.1038/s41597-020-0451-5Ovalle-Bracho C, Londoño-Barbosa D, Salgado-Almario J, González C. Evaluating the spatial distribution of Leishmania parasites in Colombia from clinical samples and human isolates (1999 to 2016). PLoS One. 2019;14. doi: 10.1371/journal.pone.0214124INS IN de S. LEISHMANIASIS CUTÁNEA, MUCOSA Y VISCERAL. COLOMBIA 2018. 2018. Available: https://www.ins.gov.co/buscador-eventos/Informesdeevento/LEISHMANIASIS_2018.pdfTatu A, Radaschin D. A short review about cutaneous microbiome. 2018;41: 237–241. doi: 10.35219/ann-ugal-math-phys-mec.2018.2.17Baldwin HE, Bhatia ND, Friedman A, Eng RM, Seite S. The Role of Cutaneous Microbiota Harmony in Maintaining a Functional Skin Barrier. J Drugs Dermatol. 2017;16: 12–18.Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16: 143–155. doi: 10.1038/nrmicro.2017.157De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms. 2021;9. doi: 10.3390/microorganisms9020353Ederveen THA, Smits JPH, Boekhorst J, Schalkwijk J, van den Bogaard EH, Zeeuwen PLJM. Skin microbiota in health and disease: From sequencing to biology. J Dermatol. 2020;47: 1110–1118. doi: 10.1111/1346-8138.15536Flowers L, Grice EA. The Skin Microbiota: Balancing Risk and Reward. Cell Host Microbe. 2020;28: 190–200. doi: 10.1016/j.chom.2020.06.017Loomis KH, Wu SK, Ernlund A, Zudock K, Reno A, Blount K, et al. A mixed community of skin microbiome representatives influences cutaneous processes more than individual members. Microbiome. 2021;9: 22. doi: 10.1186/s40168-020-00963-1Assarsson M, Duvetorp A, Dienus O, Söderman J, Seifert O. Significant Changes in the Skin Microbiome in Patients with Chronic Plaque Psoriasis after Treatment with Narrowband Ultraviolet B. Acta Derm Venereol. 2018;98: 428–436. doi: 10.2340/00015555-2859Baviera G, Leoni MC, Capra L, Cipriani F, Longo G, Maiello N, et al. Microbiota in Healthy Skin and in Atopic Eczema. Biomed Res Int. 2014;2014: 436921. doi: 10.1155/2014/436921Bjerre RD, Bandier J, Skov L, Engstrand L, Johansen JD. The role of the skin microbiome in atopic dermatitis: a systematic review. British Journal of Dermatology. 2017;177: 1272–1278. doi: 10.1111/bjd.15390Chen L, Li J, Zhu W, Kuang Y, Liu T, Zhang W, et al. Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies. Front Microbiol. 2020;11: 589726. doi: 10.3389/fmicb.2020.589726Fyhrquist N, Muirhead G, Prast-Nielsen S, Jeanmougin M, Olah P, Skoog T, et al. Microbe-host interplay in atopic dermatitis and psoriasis. Nat Commun. 2019;10: 4703. doi: 10.1038/s41467-019-12253-yPicardo M, Ottaviani M. Skin microbiome and skin disease: the example of rosacea. J Clin Gastroenterol. 2014;48 Suppl 1: S85–86. doi: 10.1097/MCG.0000000000000241Ring HC, Thorsen J, Saunte DM, Lilje B, Bay L, Riis PT, et al. The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls. JAMA Dermatol. 2017;153: 897–905. doi: 10.1001/jamadermatol.2017.0904Oliveira MR de, Tafuri WL, Nicoli JR, Vieira EC, Melo MN, Vieira LQ. Influence of microbiota in experimental cutaneous leishmaniasis in swiss MICE. Rev Inst Med trop S Paulo. 1999;41: 87–94. doi: 10.1590/s0036-46651999000200005Ec V, Jr N, T M-S, Me S, Ca da C, W M, et al. Cutaneous leishmaniasis in germfree, gnotobiotic, and conventional mice. Revista do Instituto de Medicina Tropical de Sao Paulo. 1987;29. doi: 10.1590/s0036-46651987000600009Gimblet C, Meisel JS, Loesche MA, Cole SD, Horwinski J, Novais FO, et al. Cutaneous leishmaniasis induces a transmissible dysbiotic skin microbiota that promotes skin inflammation. Cell Host Microbe. 2017;22: 13–24.e4. doi: 10.1016/j.chom.2017.06.006Salgado VR, Queiroz ATL de, Sanabani SS, Oliveira CI de, Carvalho EM, Costa JML, et al. The microbiological signature of human cutaneous leishmaniasis lesions exhibits restricted bacterial diversity compared to healthy skin. Mem Inst Oswaldo Cruz. 2016;111: 241–251. doi: 10.1590/0074-02760150436Ereqat S, Al-Jawabreh A, Abdeen Z, Al-Jawabreh H, Nasereddin A. Characterization of Leishmania Ulcers Microbiota Using Next-Generation Sequencing. Al-Quds Acad Res. 2021. doi: 10.47874/2021p8Jayasena Kaluarachchi TD, Campbell PM, Wickremasinghe R, Ranasinghe S, Wickremasinghe R, Yasawardene S, et al. Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds. Sci Rep. 2021;11: 23181. doi: 10.1038/s41598-021-02388-8Amorim CF, Lovins VM, Singh TP, Novais FO, Harris JC, Lago AS, et al. Multi-omic profiling of cutaneous leishmaniasis infections reveals microbiota-driven mechanisms underlying disease severity. medRxiv; 2023. p. 2023.02.02. doi: 10.1101/2023.02.02.23285247Beiter KJ, Wentlent ZJ, Hamouda AR, Thomas BN. Nonconventional opponents: a review of malaria and leishmaniasis among United States Armed Forces. PeerJ. 2019;7: e6313. doi: 10.7717/peerj.6313Hernández AM, Gutierrez JD, Xiao Y, Branscum AJ, Cuadros DF. Spatial epidemiology of cutaneous leishmaniasis in Colombia: socioeconomic and demographic factors associated with a growing epidemic. Transactions of The Royal Society of Tropical Medicine and Hygiene. 2019;113: 560–568. doi: 10.1093/trstmh/trz043Requena JM, Chicharro C, García L, Parrado R, Puerta CJ, Cañavate C. Sequence analysis of the 3’-untranslated region of HSP70 (type I) genes in the genus Leishmania: its usefulness as a molecular marker for species identification. Parasites & Vectors. 2012;5: 87. doi: 10.1186/1756-3305-5-87Ramírez CA, Requena JM, Puerta CJ. Identification of the HSP70-II gene in Leishmania braziliensis HSP70 locus: genomic organization and UTRs characterization. Parasites & Vectors. 2011;4: 166. doi: 10.1186/1756-3305-4-166Hernández C, Alvarez C, González C, Ayala MS, León CM, Ramírez JD. Identification of six New World Leishmania species through the implementation of a High-Resolution Melting (HRM) genotyping assay. Parasit Vectors. 2014;7: 501. doi: 10.1186/s13071-014-0501-yFraga J, Montalvo AM, De Doncker S, Dujardin J-C, Van der Auwera G. Phylogeny of Leishmania species based on the heat-shock protein 70 gene. Infect Genet Evol. 2010;10: 238–245. doi: 10.1016/j.meegid.2009.11.007Akhoundi M, Kuhls K, Cannet A, Votýpka J, Marty P, Delaunay P, et al. A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies. PLoS Negl Trop Dis. 2016;10: e0004349. doi: 10.1371/journal.pntd.0004349WMA—The World Medical Association-Declaración de Helsinki de la AMM–Principios éticos para las investigaciones médicas en seres humanos. [cited 22 Sep 2023]. Available: https://www.wma.net/es/policies-post/declaracion-de-helsinki-de-la-amm-principios-eticos-para-las-investigaciones-medicas-en-seres-humanos/INS IN de S. Protocolo de Vigilancia de Leishmaniasis. INS; 2022. Available: https://www.ins.gov.co/buscador-eventos/Lineamientos/PRO_Leishmaniasis.pdfOPS OP de la S. Manual de procedimientos para vigilancia y control de las leishmaniasis en las Américas. 1st ed. Washington, D.C.: OPS; 2019. Available: 10.37774/9789275320631Klymiuk I, Bambach I, Patra V, Trajanoski S, Wolf P. 16S Based Microbiome Analysis from Healthy Subjects’ Skin Swabs Stored for Different Storage Periods Reveal Phylum to Genus Level Changes. Front Microbiol. 2016;7: 2012. doi: 10.3389/fmicb.2016.02012Novogene. 16S/18S/ITS Amplicon Metagenomic Sequencing. In: Novogene [Internet]. [cited 26 Oct 2021]. Available: https://en.novogene.com/16s-18s-its-amplicon-metagenomic-sequencing/Ramírez JD, Cao L, Castillo-Castañeda AC, Patino LH, Ayala MS, Cordon-Cardo C, et al. Clinical performance of a quantitative pan-genus Leishmania Real-time PCR assay for diagnosis of cutaneous and visceral leishmaniasis. Practical Laboratory Medicine. 2023;37: e00341. doi: 10.1016/j.plabm.2023.e00341Patiño LH, Castillo-Castañeda A, Muñoz M, Jaimes J, Luna N, Hernández C, et al. Development of an amplicon-based Next Generation Sequencing protocol to identify Leishmania species and other trypanosomatids in Leishmaniasis endemic areas. Microbiol Spectr. 2021;(article accepted for publication). doi: 10.1128/Spectrum.00652-21Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, et al. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486: 207–214. doi: 10.1038/nature11234Vega L, Herrera G, Muñoz M, Patarroyo MA, Maloney JG, Santín M, et al. Gut microbiota profiles in diarrheic patients with co-occurrence of Clostridioides difficile and Blastocystis. PLOS ONE. 2021;16: e0248185. doi: 10.1371/journal.pone.0248185Herrera G, Vega L, Patarroyo MA, Ramírez JD, Muñoz M. Gut microbiota composition in health-care facility-and community-onset diarrheic patients with Clostridioides difficile infection. Sci Rep. 2021;11: 10849. doi: 10.1038/s41598-021-90380-7Andrews S. Babraham Bioinformatics—FastQC A Quality Control tool for High Throughput Sequence Data. [cited 26 Oct 2021]. Available: https://www.bioinformatics.babraham.ac.uk/projects/fastqc/Ewels P, Magnusson M, Lundin S, Käller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016;32: 3047–3048. doi: 10.1093/bioinformatics/btw354Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37: 852–857. doi: 10.1038/s41587-019-0209-9Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13: 581–583. doi: 10.1038/nmeth.3869Sfriso R, Egert M, Gempeler M, Voegeli R, Campiche R. Revealing the secret life of skin—with the microbiome you never walk alone. International Journal of Cosmetic Science. 2020;42: 116–126. doi: 10.1111/ics.12594Boxberger M, Cenizo V, Cassir N, La Scola B. Challenges in exploring and manipulating the human skin microbiome. Microbiome. 2021;9: 125. doi: 10.1186/s40168-021-01062-5Carmona-Cruz S, Orozco-Covarrubias L, Sáez-de-Ocariz M. The Human Skin Microbiome in Selected Cutaneous Diseases. Frontiers in Cellular and Infection Microbiology. 2022;12. Available: https://www.frontiersin.org/articles/10.3389/fcimb.2022.834135Patiño LH, Castillo-Castañeda AC, Muñoz M, Jaimes JE, Luna-Niño N, Hernández C, et al. Development of an Amplicon-Based Next-Generation Sequencing Protocol to Identify Leishmania Species and Other Trypanosomatids in Leishmaniasis Endemic Areas. Microbiol Spectr. 2021; e0065221. doi: 10.1128/Spectrum.00652-21Castillo-Castañeda A, Patiño LH, Muñoz M, Ayala MS, Segura M, Bautista J, et al. Amplicon-based next-generation sequencing reveals the co-existence of multiple Leishmania species in patients with visceral leishmaniasis. Int J Infect Dis. 2022;115: 35–38. doi: 10.1016/j.ijid.2021.11.029Cantanhêde LM, Cupolillo E. Leishmania (Viannia) naiffi Lainson & Shaw 1989. Parasit Vectors. 2023;16: 194. doi: 10.1186/s13071-023-05814-0Pratlong F, Deniau M, Darie H, Eichenlaub S, Pröll S, Garrabe E, et al. Human cutaneous leishmaniasis caused by Leishmania naiffi is wide-spread in South America. Ann Trop Med Parasitol. 2002;96: 781–785. doi: 10.1179/000349802125002293van der Snoek EM, Lammers AM, Kortbeek LM, Roelfsema JH, Bart A, Jaspers C a JJ. Spontaneous cure of American cutaneous leishmaniasis due to Leishmania naiffi in two Dutch infantry soldiers. Clin Exp Dermatol. 2009;34: e889–891. doi: 10.1111/j.1365-2230.2009.03658.xAlexandre J, Sadlova J, Lestinova T, Vojtkova B, Jancarova M, Podesvova L, et al. Experimental infections and co-infections with Leishmania braziliensis and Leishmania infantum in two sand fly species, Lutzomyia migonei and Lutzomyia longipalpis. Sci Rep. 2020;10: 3566. doi: 10.1038/s41598-020-60600-7Se G, Sl H, K H, Ja S, Ea G. The neuropathic diabetic foot ulcer microbiome is associated with clinical factors. Diabetes. 2013;62. doi: 10.2337/db12-0771Mudrik-Zohar H, Carasso S, Gefen T, Zalmanovich A, Katzir M, Cohen Y, et al. Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods. Frontiers in Cellular and Infection Microbiology. 2022;12. Available: https://www.frontiersin.org/articles/10.3389/fcimb.2022.836699Hershko AY. Insights into the mast cell-microbiome connection in the skin. J Allergy Clin Immunol. 2017;139: 1137–1139. doi: 10.1016/j.jaci.2016.11.016Camanocha A, Dewhirst FE. Host-associated bacterial taxa from Chlorobi, Chloroflexi, GN02, Synergistetes, SR1, TM7, and WPS-2 Phyla/candidate divisions. J Oral Microbiol. 2014;6. doi: 10.3402/jom.v6.25468Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner ACR, Yu W-H, et al. The human oral microbiome. J Bacteriol. 2010;192: 5002–5017. doi: 10.1128/JB.00542-10Sedghi L, DiMassa V, Harrington A, Lynch SV, Kapila YL. The oral microbiome: Role of key organisms and complex networks in oral health and disease. Periodontology 2000. 2021;87: 107. doi: 10.1111/prd.12393Irfan M, Delgado RZR, Frias-Lopez J. The Oral Microbiome and Cancer. Frontiers in Immunology. 2020;11. doi: 10.3389/fimmu.2020.591088Misra P, Singh S. Site specific microbiome of Leishmania parasite and its cross-talk with immune milieu. Immunol Lett. 2019;216: 79–88. doi: 10.1016/j.imlet.2019.10.004A P, Rw J, M O, Lv C, P S, G N, et al. Staphylococcus aureus resistance to human defensins and evasion of neutrophil killing via the novel virulence factor MprF is based on modification of membrane lipids with l-lysine. The Journal of experimental medicine. 2001;193. doi: 10.1084/jem.193.9.1067Peschel A, Otto M, Jack RW, Kalbacher H, Jung G, Götz F. Inactivation of the dlt Operon inStaphylococcus aureus Confers Sensitivity to Defensins, Protegrins, and Other Antimicrobial Peptides*. Journal of Biological Chemistry. 1999;274: 8405–8410. doi: 10.1074/jbc.274.13.8405Charmoy M, Hurrell BP, Romano A, Lee SH, Ribeiro-Gomes F, Riteau N, et al. The Nlrp3 inflammasome, IL-1β, and neutrophil recruitment are required for susceptibility to a nonhealing strain of Leishmania major in C57BL/6 mice. European Journal of Immunology. 2016;46: 897–911. doi: 10.1002/eji.201546015Singh TP, Carvalho AM, Sacramento LA, Grice EA, Scott P. Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis. PLOS Pathogens. 2021;17: e1009693. doi: 10.1371/journal.ppat.1009693Shalon D, Culver RN, Grembi JA, Folz J, Treit PV, Shi H, et al. Profiling the human intestinal environment under physiological conditions. Nature. 2023;617: 581–591. doi: 10.1038/s41586-023-05989-Meisel JS, Sfyroera G, Bartow-McKenney C, Gimblet C, Bugayev J, Horwinski J, et al. Commensal microbiota modulate gene expression in the skin. Microbiome. 2018;6: 20. doi: 10.1186/s40168-018-0404-9Naik S, Bouladoux N, Linehan JL, Han S-J, Harrison OJ, Wilhelm C, et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature. 2015;520: 104–108. doi: 10.1038/nature14052Liu C, Ponsero AJ, Armstrong DG, Lipsky BA, Hurwitz BL. The dynamic wound microbiome. BMC Medicine. 2020;18: 358. doi: 10.1186/s12916-020-01820-6Verbanic S, Shen Y, Lee J, Deacon JM, Chen IA. Microbial predictors of healing and short-term effect of debridement on the microbiome of chronic wounds. npj Biofilms Microbiomes. 2020;6: 1–11. doi: 10.1038/s41522-020-0130-5Isaac-Márquez AP, Lezama-Dávila CM. Detection of pathogenic bacteria in skin lesions of patients with chiclero’s ulcer: reluctant response to antimonial treatment. Mem Inst Oswaldo Cruz. 2003;98: 1093–1095. doi: 10.1590/S0074-02762003000800021Fontes CO, Carvalho MAR, Nicoli JR, Hamdan JS, Mayrink W, Genaro O, et al. Identification and antimicrobial susceptibility of micro-organisms recovered from cutaneous lesions of human American tegumentary leishmaniasis in Minas Gerais, Brazil. J Med Microbiol. 2005;54: 1071–1076. doi: 10.1099/jmm.0.46070-0Antonio L de F, Lyra MR, Saheki MN, Schubach A de O, Miranda L de FC, Madeira M de F, et al. Effect of secondary infection on epithelialisation and total healing of cutaneous leishmaniasis lesions. Mem Inst Oswaldo Cruz. 2017;112: 640–646. doi: 10.1590/0074-02760160557Layegh P, Ghazvini K, Moghiman T, Hadian F, Zabolinejad N, Pezeshkpour F. Bacterial Contamination in Cutaneous Leishmaniasis: Its Effect on the Lesions’ Healing Course. Indian J Dermatol. 2015;60: 211. doi: 10.4103/0019-5154.152560Bk P, Kh P, Ry H, Cn L, Sm M. The Gut-Skin Microbiota Axis and Its Role in Diabetic Wound Healing-A Review Based on Current Literature. International journal of molecular sciences. 2022;23. doi: 10.3390/ijms23042375Olejniczak-Staruch I, Ciążyńska M, Sobolewska-Sztychny D, Narbutt J, Skibińska M, Lesiak A. Alterations of the Skin and Gut Microbiome in Psoriasis and Psoriatic Arthritis. Int J Mol Sci. 2021;22: 3998. doi: 10.3390/ijms22083998A O. [Corynebacterium-associated skin infections]. Annales de dermatologie et de venereologie. 2018;145. doi: 10.1016/j.annder.2018.01.039Dréno B, Dagnelie MA, Khammari A, Corvec S. The Skin Microbiome: A New Actor in Inflammatory Acne. Am J Clin Dermatol. 2020;21: 18–24. doi: 10.1007/s40257-020-00531-1Guerrero DM, Perez F, Conger NG, Solomkin JS, Adams MD, Rather PN, et al. Acinetobacter baumannii-Associated Skin and Soft Tissue Infections: Recognizing a Broadening Spectrum of Disease*. Surg Infect (Larchmt). 2010;11: 49–57. doi: 10.1089/sur.2009.022Reina R, León-Moya C, Garnacho-Montero J. Treatment of Acinetobacter baumannii severe infections. Med Intensiva (Engl Ed). 2022;46: 700–710. doi: 10.1016/j.medine.2022.08.007Zhang J, Zheng Y-C, Chu Y-L, Cui X-M, Wei R, Bian C, et al. Skin infectome of patients with a tick bite history. Front Cell Infect Microbiol. 2023;13: 1113992. doi: 10.3389/fcimb.2023.1113992Willmott T, Campbell PM, Griffiths CEM, O’Connor C, Bell M, Watson REB, et al. Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity. Front Aging. 2023;4: 1217635. doi: 10.3389/fragi.2023.1217635H E, Hb T, Mwj S, B B, Ri T, Sr K, et al. Depletion of Saccharomyces cerevisiae in psoriasis patients, restored by Dimethylfumarate therapy (DMF). PloS one. 2017;12. doi: 10.1371/journal.pone.0176955S H, C P, J B, S R, Z K, A M, et al. Saccharomyces cerevisiae as a skin physiology, pathology, and treatment model. Dermatology online journal. 2020;26. Available: https://pubmed.ncbi.nlm.nih.gov/33342171/Díaz MGU, Uzcátegui AM, Sáenz AM, Solano M. Microbiota, microbioma y su manipulación en enfermedades de la piel. Dermatología Venezolana. 2020;58. Available: https://revista.svderma.org/index.php/ojs/article/view/1468Rincón S, Celis A, Sopó L, Motta A, García MCC de. Malassezia yeast species isolated from patients with dermatologic lesions. Biomédica. 2005;25: 189–95. doi: 10.7705/biomedica.v25i2.1341Lind AL, Pollard KS. Accurate and sensitive detection of microbial eukaryotes from whole metagenome shotgun sequencing. Microbiome. 2021;9: 58. doi: 10.1186/s40168-021-01015-yCelis AM, García MCC de. Genetic polymorphism of Malassezia spp. yeast isolates from individuals with and without dermatological lesions. Biomédica. 2005;25: 481–7. doi: 10.7705/biomedica.v25i4.1374Sommer B, Overy DP, Kerr RG. Identification and characterization of lipases from Malassezia restricta, a causative agent of dandruff. FEMS Yeast Research. 2015;15: fov078. doi: 10.1093/femsyr/fov078Hadrich I, Khemakhem N, Ilahi A, Trabelsi H, Sellami H, Makni F, et al. Genotypic Analysis of the Population Structure in Malassezia globosa and Malassezia restricta. J Fungi (Basel). 2023;9: 263. doi: 10.3390/jof9020263Green BJ. Emerging Insights into the Occupational Mycobiome. Curr Allergy Asthma Rep. 2018;18: 62. doi: 10.1007/s11882-018-0818-2D L, O A, Ce E. Approach to chronic wound infections. The British journal of dermatology. 2015;173. doi: 10.1111/bjd.13677Gardiner M, Vicaretti M, Sparks J, Bansal S, Bush S, Liu M, et al. A longitudinal study of the diabetic skin and wound microbiome. PeerJ. 2017;5: e3543. doi: 10.7717/peerj.3543Dowd SE, Sun Y, Secor PR, Rhoads DD, Wolcott BM, James GA, et al. Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC Microbiol. 2008;8: 43. doi: 10.1186/1471-2180-8-43Rd W, Jd H, Ej R, Ld K, Cd P, Ra W, et al. Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society. 2016;24. doi: 10.1111/wrr.12370M L, Se G, L K, J H, Q Z, Bp H, et al. Temporal Stability in Chronic Wound Microbiota Is Associated With Poor Healing. The Journal of investigative dermatology. 2017;137. doi: 10.1016/j.jid.2016.08.009Kalan LR, Meisel JS, Loesche MA, Horwinski J, Soaita I, Chen X, et al. Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy. Cell Host Microbe. 2019;25: 641–655.e5. doi: 10.1016/j.chom.2019.03.006Rahim K, Saleha S, Zhu X, Huo L, Basit A, Franco OL. Bacterial Contribution in Chronicity of Wounds. Microb Ecol. 2017;73: 710–721. doi: 10.1007/s00248-016-0867-9Jneid J, Cassir N, Schuldiner S, Jourdan N, Sotto A, Lavigne J-P, et al. Exploring the Microbiota of Diabetic Foot Infections With Culturomics. Front Cell Infect Microbiol. 2018;8: 282. doi: 10.3389/fcimb.2018.00282Ammons MCB, Morrissey K, Tripet BP, Van Leuven JT, Han A, Lazarus GS, et al. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds. PLoS One. 2015;10: e0126735. doi: 10.1371/journal.pone.0126735instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURMicrobiomaMicrobiotaProcariotasEucariotasPielLeishmaniasis CutáneaMicrobiomeMicrobiotaProkaryotesEukaryotesSkinCutaneous LeishmaniasisModificaciones de la microbiota cutánea de procariota y eucariota desencadenadas por la infección por Leishmania en la leishmaniasis cutánea localizadaProkaryotic and eukaryotic skin microbiota modifications triggered by Leishmania infection in localized Cutaneous LeishmaniasisbachelorThesisArtículoArtículohttp://purl.org/coar/resource_type/c_7a1fFacultad de Ciencias NaturalesBogotáLICENSElicense.txtlicense.txttext/plain1483https://repository.urosario.edu.co/bitstreams/f9b4922b-74db-4db1-b03d-c745992e4fc2/downloadb2825df9f458e9d5d96ee8b7cd74fde6MD54CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8899https://repository.urosario.edu.co/bitstreams/82469cfd-c0bc-4ae4-88e0-b19d44941a4c/download3b6ce8e9e36c89875e8cf39962fe8920MD55ORIGINALModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.pdfModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.pdfapplication/pdf1542011https://repository.urosario.edu.co/bitstreams/1654a095-71a1-4246-b01f-356a8ae85aa3/downloade22128b5e5c3330aefd59010ab2c3c70MD57Modificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.zipModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.zip application/zip121251874https://repository.urosario.edu.co/bitstreams/36496856-330b-4700-909e-b71dc4116852/download5791b9e6ca95c4e9c7ac1a4a43864170MD56TEXTModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.pdf.txtModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.pdf.txtExtracted texttext/plain100306https://repository.urosario.edu.co/bitstreams/08bd3e0e-ceb9-40e5-81c1-b264aa77ee90/downloade6407e96e73400b9bdc36142681c9a31MD58THUMBNAILModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.pdf.jpgModificaciones_de_la microbiota_cutanea_de_procariota_y_eucariota_JaimesSilva-JesusEduardo-2024.pdf.jpgGenerated Thumbnailimage/jpeg2107https://repository.urosario.edu.co/bitstreams/8bf2e89f-3e08-43c3-9e23-f5a234069863/downloadca7c46d644ef1bad9754f9a89ee31d7aMD5910336/43490oai:repository.urosario.edu.co:10336/434902024-10-05 03:03:14.659http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttps://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.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