Estudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapia

Vista sencilla de ítem
dc.contributor.advisorSoto Ospina, Carlos Yesid
dc.contributor.authorChavarro Portillo, Bibiana
dc.contributor.orcidhttps://orcid.org/0000-0001-7186-2028spa
dc.contributor.projectleaderGuerrero Guerrero Martha Inirida
dc.contributor.researchgatehttps://www.researchgate.net/profile/Bibiana-Chavarro-Portillospa
dc.contributor.researchgroupBioquímica y Biología Molecular de las Micobacteriasspa
dc.date.accessioned2023-06-01T13:03:48Z
dc.date.available2023-06-01T13:03:48Z
dc.date.issued2021-07-26
dc.descriptionilustraciones, graficas
dc.description.abstractLa lepra es una enfermedad dermato-neurológica crónica, causada por Mycobacterium leprae, que en Colombia causa cerca de 400 casos nuevos cada año. La lepra se trata con una poliquimioterapia (PQT) y su eficacia es establecida por el seguimiento de casos recurrentes de la enfermedad. Debido a que la recurrencia no puede ser diferenciada en recaída o reinfección clínicamente, en el presente estudio, usamos técnicas de secuenciación total de ADN (genoma) y ARN (transcriptoma), con el fin de conocer algunas características genómicas y transcriptómicas de cepas de M. leprae asociadas con múltiples episodios de lepra post-PQT en Colombia. A partir de biopsias provenientes del diagnóstico inicial y durante la recurrencia de la enfermedad, se aisló ADN y se realizó la secuenciación total de genomas de M. leprae causantes de cada evento y se analizaron in silico los conjuntos de secuencias resultantes. Los análisis de genómica comparativa de las cepas de M. leprae causantes de eventos recurrentes permitieron establecer tres hallazgos importantes: i) encontrar ciertas características genómicas que podrían diferenciar una recaída de una recaída y reinfección, ii) la relación genética entre cepas colombianas y cepas antiguas y modernas , además de cepas aisladas en otros hospederos, como el armadillo de nueve bandas y ardillas de cola roja y iii) establecer posibles efectos de las mutaciones identificadas en los genomas analizados. Por otra parte, también se pudo establecer la capacidad infectiva de cepas de M. leprae relacionadas con un evento inicial en comparación con cepas asociadas a eventos recurrentes en un modelo in vitro de infección de células de Schwann. Se pudo observar que la entrada inicial de M. leprae a las células de Schwann no depende de las características inherentes de las cepas (vivas o muertas, de pacientes de eventos recurrentes o nuevos) ni de la carga bacteriana usada para la infección; pero la capacidad de infectar más células a través del tiempo si depende de la viabilidad del bacilo. Los análisis transcripcionales muestran la actividad de genes involucrados en la virulencia y supervivencia, además de los genes codificantes de proteínas de choque térmico, los cuales favorecen la supervivencia de M. leprae en condiciones de estrés o durante el cultivo in vitro. Como un marcador de patogenicidad, mediante qPCR, se evaluaron los niveles de expresión de siete genes implicados en la síntesis de PGL-1 durante la infección de células de Schwann. Los resultados mostraron una expresión diferencial de ciertos genes que se sugieren una capacidad metabólica disminuida en el caso de M. leprae provenientes de pacientes con recaída. (Texto tomado de la fuente)spa
dc.description.abstractLeprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae, which in Colombia causes about 400 new cases each year. Leprosy is treated with multidrug therapy (MDT) or polychemotherapy (PQT), and its efficacy is established by monitoring recurrent cases of the disease. Because recurrence cannot be clinically differentiated into relapse or reinfection, in the present study, we used total DNA (genome) and RNA (transcriptome) sequencing technique, in order to know some genomic and transcriptomic characteristics of M. leprae strains associated with multiple episodes of post-PQT leprosy in Colombia. From biopsies of initial diagnosis and during disease recurrence, DNA was isolated, and total genomes of M. leprae causing each event were sequence. The resulting sets of sequences were analyzed in silico. The comparative genomic analyzes of the M. leprae strains causing recurrent events allowed to us stablish three important findings: i) find certain genomic characteristics that could differentiate between relapse and reinfection, ii) the genetic relationship between Colombian strains and ancient, modern strains and strains isolated in other hosts, non-humans and iii) establish possible effects of the mutations identified in the genomes analyzed. An in vitro model of Schwann cell infection could establish the infective capacity of M. leprae strains from initial events compared to strains associated with recurrent events. It could be observed that the initial entry of M. leprae into Schwann cells does not depend on the inherent characteristics of the strains of patients with recurrent or new events or the bacterial load used for infection; but the ability to infect more cells over time depends on the genomic or metabolic characteristics of the bacillus. Transcriptional analyzes show the activity of genes involved in survival, in addition to genes encoding heat shock proteins, which favor the survival of M. leprae under stress conditions or during in vitro culture. As a marker of pathogenicity, by means of qPCR, the expression levels of seven genes involved in the synthesis of PGL-1 during the infection of Schwann cells were evaluated. The results showed a differential expression of certain genes that suggest a decreased metabolic capacity in the case of M. leprae from patients with relapse.eng
dc.description.degreelevelDoctoradospa
dc.description.degreenameDoctor en Biotecnologíaspa
dc.format.extent160 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.cospa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/83938
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.programBogotá - Ciencias - Doctorado en Biotecnologíaspa
dc.relation.referencesBritton WJ, Lockwood DNJ. Leprosy. The Lancet. 2004;363: 1209–1219. doi:10.1016/S0140- 6736(04)15952-7spa
dc.relation.referencesHan XY, Seo Y-H, Sizer KC, Schoberle T, May GS, Spencer JS, et al. A New Mycobacterium Species Causing Diffuse Lepromatous Leprosy. American Journal of Clinical Pathology. 2008;130: 856–864. doi:10.1309/ajcpp72fjzzrrvmmspa
dc.relation.referencesPenna ML, Buhrer-Sekula S, Pontes MA, Cruz R, Goncalves Hde S, Penna GO. Primary results of clinical trial for uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): reactions frequency in multibacillary patients. Leprosy review. 2012;83: 308–19.spa
dc.relation.referencesScollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The Continuing Challenges of Leprosy. Clinical Microbiology Reviews. 2006;19: 338. doi:10.1128/cmr.19.2.338- 381.2006spa
dc.relation.referencesWHO. Global leprosy update, 2017: reducing the disease burden due to leprosy. Weekly epidemiological record. 2018;93: 444–456.spa
dc.relation.referencesInstituto Nacional de Salud. LEPRA, Periodo epidemiológico XIII. Colombia, 2019. 2019; Bogotá DC, Colombia. Available: https://www.ins.gov.co/buscador- eventos/Informesdeevento/LEPRA%20PE%20XIII%202019.pdfspa
dc.relation.referencesWHO. Global leprosy update, 2016: accelerating reduction of disease burden. Weekly epidemiological record. 2017;35: 501–520.spa
dc.relation.referencesvan Brakel WH, Post E, Saunderson PR, Gopal PK. Leprosy. In: Quah SR, editor. International Encyclopedia of Public Health (Second Edition). Oxford: Academic Press; 2017. pp. 391–401. doi:10.1016/B978-0-12-803678-5.00251-4spa
dc.relation.referencesLahiri R, Adams LB. Cultivation and Viability Determination of Mycobacterium leprae. Scollard DM, Gillis TP (ed). International textbook of leprosy. Scollard DM, Gillis TP (ed). 2016. Available: www.internationaltextbookofleprosy.org.spa
dc.relation.referencesAvanzi C, del-Pozo J, Benjak A, Stevenson K, Simpson VR, Busso P, et al. Red squirrels in the British Isles are infected with leprosy bacilli. Science. 2016;354: 744. doi:10.1126/science.aah3783spa
dc.relation.referencesHonap TP, Pfister L-A, Housman G, Mills S, Tarara RP, Suzuki K, et al. Mycobacterium leprae genomes from naturally infected nonhuman primates. PLOS Neglected Tropical Diseases. 2018;12: e0006190. doi:10.1371/journal.pntd.0006190spa
dc.relation.referencesKirchheimer WF, Storrs EE. Attempts to establish the armadillo (Dasypus novemcinctus Linn.) as a model for the study of leprosy. I. Report of lepromatoid leprosy in an experimentally infected armadillo. International journal of leprosy and other mycobacterial diseases: official organ of the International Leprosy Association. 1971;39: 693–702.spa
dc.relation.referencesNoordeen SK. Elimination of leprosy as a public health problem. Indian journal of leprosy. 1994;66: 1–10.spa
dc.relation.referencesRamos-e-Silva M, Rebello PF. Leprosy. Recognition and treatment. American journal of clinical dermatology. 2001;2: 203–11.spa
dc.relation.referencesRodrigues LC, Lockwood DNJ. Leprosy now: epidemiology, progress, challenges, and research gaps. Lancet Infect Dis. 2011;11: 464–470. doi:10.1016/s1473-3099(11)70006-8spa
dc.relation.referencesFine PE. Leprosy: the epidemiology of a slow bacterium. Epidemiologic reviews. 1982;4: 161– 88.spa
dc.relation.referencesCole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, et al. Massive gene decay in the leprosy bacillus. Nature. 2001;409: 1007–1011. doi:10.1038/35059006spa
dc.relation.referencesEiglmeier K, Parkhill J, Honore N, Garnier T, Tekaia F, Telenti A, et al. The decaying genome of Mycobacterium leprae. Leprosy review. 2001;72: 387–98.spa
dc.relation.referencesGómez-Valero L, Rocha EPC, Latorre A, Silva FJ. Reconstructing the ancestor of Mycobacterium leprae: The dynamics of gene loss and genome reduction. Genome Research. 2007;17: 1178–1185.spa
dc.relation.referencesHarrison PM, Gerstein M. Studying genomes through the aeons: protein families, pseudogenes and proteome evolution. Journal of molecular biology. 2002;318: 1155–74.spa
dc.relation.referencesLiu Y, Harrison PM, Kunin V, Gerstein M. Comprehensive analysis of pseudogenes in prokaryotes: widespread gene decay and failure of putative horizontally transferred genes. Genome biology. 2004;5: R64. doi:10.1186/gb-2004-5-9-r64spa
dc.relation.referencesMira A, Pushker R. The silencing of pseudogenes. Molecular biology and evolution. 2005;22: 2135–8. doi:10.1093/molbev/msi209spa
dc.relation.referencesWilliams DL, Slayden RA, Amin A, Martinez AN, Pittman TL, Mira A, et al. Implications of high level pseudogene transcription in Mycobacterium leprae. BMC genomics. 2009;10: 397. doi:10.1186/1471-2164-10-397spa
dc.relation.referencesChavarro-Portillo B, Soto CY, Guerrero MI. Mycobacterium leprae’s evolution and environmental adaptation. Acta Tropica. 2019;197: 105041. doi:10.1016/j.actatropica.2019.105041spa
dc.relation.referencesMitchell A, Graur D. Inferring the Pattern of Spontaneous Mutation from the Pattern of Substitution in Unitary Pseudogenes of Mycobacterium leprae and a Comparison of Mutation Patterns Among Distantly Related Organisms. Journal of Molecular Evolution. 2005;61: 795–803. doi:10.1007/s00239-004-0235-0spa
dc.relation.referencesMonot M, Honoré N, Garnier T, Zidane N, Sherafi D, Paniz-Mondolfi A, et al. Comparative genomic and phylogeographic analysis of Mycobacterium leprae. Nature Genetics. 2009;41: 1282. doi:10.1038/ng.477spa
dc.relation.referencesSingh P, Cole S. The Genomics of Leprosy. In: Nelson KE, Jones-Nelson B, editors. Genomics Applications for the Developing World. Springer New York; 2012. pp. 39–49. doi:10.1007/978-1-4614- 2182-5_4spa
dc.relation.referencesHan XY, Sizer KC, Velarde-Félix JS, Frias-Castro LO, Vargas-Ocampo F. The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico. International journal of dermatology. 2012;51: 952–959. doi:10.1111/j.1365-4632.2011.05414.xspa
dc.relation.referencesHan XY, Sizer KC, Tan HH. Identification of the leprosy agent Mycobacterium lepromatosis in Singapore. Journal of drugs in dermatology : JDD. 2012;11: 168–72.spa
dc.relation.referencesJessamine PG, Desjardins M, Gillis T, Scollard D, Jamieson F, Broukhanski G, et al. Leprosy-like illness in a patient with Mycobacterium lepromatosis from Ontario, Canada. Journal of drugs in dermatology : JDD. 2012;11: 229–33.spa
dc.relation.referencesVera-Cabrera L, Escalante-Fuentes WG, Gomez-Flores M, Ocampo-Candiani J, Busso P, Singh P, et al. Case of diffuse lepromatous leprosy associated with “Mycobacterium lepromatosis.” Journal of clinical microbiology. 2011;49: 4366–4368. doi:10.1128/jcm.05634-11spa
dc.relation.referencesSingh P, Benjak A, Schuenemann VJ, Herbig A, Avanzi C, Busso P, et al. Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis. Proceedings of the National Academy of Sciences of the United States of America. 2015;112: 4459–4464. doi:10.1073/pnas.1421504112spa
dc.relation.referencesCole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998;393: 537–44. doi:10.1038/31159spa
dc.relation.referencesStinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, et al. Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome research. 2008;18: 729–41. doi:10.1101/gr.075069.107spa
dc.relation.referencesStinear TP, Seemann T, Pidot S, Frigui W, Reysset G, Garnier T, et al. Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer. Genome research. 2007;17: 192–200. doi:10.1101/gr.5942807spa
dc.relation.referencesSingh P, Tufariello J, Wattam AR, Gillis TP, Jacobs Jr WR. Genomics Insights into the Biology and Evolution of Leprosy Bacilli. Scollard DM, Gillis TP (ed). International textbook of leprosy. Scollard DM, Gillis TP (ed). 2018. Available: www.internationaltextbookofleprosy.orgspa
dc.relation.referencesComas I, Homolka S, Niemann S, Gagneux S. Genotyping of Genetically Monomorphic Bacteria: DNA Sequencing in Mycobacterium tuberculosis Highlights the Limitations of Current Methodologies. PLOS ONE. 2009;4: e7815. doi:10.1371/journal.pone.0007815spa
dc.relation.referencesBenjak A, Avanzi C, Singh P, Loiseau C, Girma S, Busso P, et al. Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nature Communications. 2018;9: 352. doi:10.1038/s41467-017-02576-zspa
dc.relation.referencesMonot M, Honoré N, Garnier T, Araoz R, Coppée J-Y, Lacroix C, et al. On the Origin of Leprosy. Science. 2005;308: 1040. doi:10.1126/science/1109759spa
dc.relation.referencesSingh P, Cole ST. Mycobacterium leprae: genes, pseudogenes and genetic diversity. Future Microbiology. 2011;6: 57–71. doi:10.2217/fmb.10.153spa
dc.relation.referencesGillis T, Vissa V, Matsuoka M, Young S, Richardus JH, Truman R, et al. Characterisation of short tandem repeats for genotyping Mycobacterium leprae. Lepr Rev. 2009;80: 250–260.spa
dc.relation.referencesSalipante SJ, Hall BG. Towards the molecular epidemiology of Mycobacterium leprae: Strategies, successes, and shortcomings. Infection, Genetics and Evolution. 2011;11: 1505–1513. doi:10.1016/j.meegid.2011.06.003spa
dc.relation.referencesSchuenemann VJ, Singh P, Mendum TA, Krause-Kyora B, Jäger G, Bos KI, et al. Genome-Wide Comparison of Medieval and Modern Mycobacterium leprae. Science. 2013;341: 179. doi:10.1126/science.1238286spa
dc.relation.referencesSingh P, Benjak A, Carat S, Kai M, Busso P, Avanzi C, et al. Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3. Clinical Microbiology and Infection. 2014;20: O619–O622. doi:10.1111/1469-0691.12609spa
dc.relation.referencesTruman RW, Singh P, Sharma R, Busso P, Rougemont J, Paniz-Mondolfi A, et al. Probable zoonotic leprosy in the southern United States. The New England journal of medicine. 2011;364: 1626– 1633. doi:10.1056/NEJMoa1010536spa
dc.relation.referencesSharma R, Singh P, Loughry WJ, Lockhart JM, Inman WB, Duthie MS, et al. Zoonotic Leprosy in the Southeastern United States. Emerging infectious diseases. 2015;21: 2127–2134. doi:10.3201/eid2112.150501spa
dc.relation.referencesSchuenemann VJ, Avanzi C, Krause-Kyora B, Seitz A, Herbig A, Inskip S, et al. Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe. PLOS Pathogens. 2018;14: e1006997. doi:10.1371/journal.ppat.1006997spa
dc.relation.referencesCardona-Castro N, Beltran-Alzate JC, Romero-Montoya IM, Melendez E, Torres F, Sakamuri RM, et al. Identification and comparison of Mycobacterium leprae genotypes in two geographical regions of Colombia. Leprosy review. 2009;80: 316–21.spa
dc.relation.referencesCardona-Castro N, Beltrán-Alzate JC, Romero-Montoya IM, Li W, Brennan PJ, Vissa V. Mycobacterium leprae in Colombia described by SNP7614 in gyrA, two minisatellites and geography. Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases. 2013;14: 375–382. doi:10.1016/j.meegid.2012.12.015spa
dc.relation.referencesTorres-Ávila JF, Colorado CL, Gamboa LA, Araujo MJ, León-Franco CI, Guerrero-Guerrero MI. Genotipificación de Mycobacterium leprae Colombiano para la Determinación de Patrones de Transmisión de la Enfermedad. Revista de Salud Pública. 2009;11: 3–13.spa
dc.relation.referencesScollard DM, Truman RW, Ebenezer GJ. Mechanisms of nerve injury in leprosy. Clin Dermatol. 2015;33: 46–54. doi:10.1016/j.clindermatol.2014.07.008spa
dc.relation.referencesMuvdi-Arenas S, Ordóñez-Rubiano M. Aspectos clínicos. La lepra: una enfermedad vigente En: Guerrero MI, Hernández CA y Rodríguez G Editores Centro Dermatológico Federico Lleras Acosta Bogotá DC, Colombia Panamericana Formas e Impresos. 2019. pp. 89-114.spa
dc.relation.referencesRidley DS, Jopling WH. Classification of leprosy according to immunity. A five-group system. International journal of leprosy and other mycobacterial diseases: official organ of the International Leprosy Association. 1966;34: 255–73.spa
dc.relation.referencesWalker SL, Lockwood DNJ. Leprosy. Clinics in Dermatology. 2007;25: 165–172. doi:10.1016/j.clindermatol.2006.05.012spa
dc.relation.referencesNordeen SK. The epidemiology of leprosy. Edinburgh, United Kingdom: Churchill-Livingstone; 1985.spa
dc.relation.referencesWHO. Global leprosy update, 2018: moving towards a leprosy free world. Weekly epidemiological record. 2019;94: 389–412.spa
dc.relation.referencesWHO - Global Leprosy Programme. Global Leprosy Strategy 2016-2020: Accelerating towards a leprosy-free world. 2016; 20.spa
dc.relation.referencesIQUEN. Situación epidemiológica de lepra, Colombia, 2012 a 2014. Informe Quincenal Epidemiológico Nacional. 2015;20.spa
dc.relation.referencesGuerrero MI, Muvdi S, León CI. Retraso en el diagnóstico de lepra como factor pronostico de discapacidad en una cohorte de pacientes en Colombia, 2000 - 2010. Revista Panamericana de Salud Pública. 2013;33: 137–143.spa
dc.relation.referencesVirmond M, Grzybowski A, Virmond L. Leprosy: A glossary. Clin Dermatol. 2015;33: 8–18. doi:10.1016/j.clindermatol.2014.07.006spa
dc.relation.referencesMisch EA, Berrington WR, Vary JC, Hawn TR. Leprosy and the Human Genome. Microbiology and Molecular Biology Reviews : MMBR. 2010;74: 589–620. doi:10.1128/mmbr.00025-10spa
dc.relation.referencesNath I, Saini C, Valluri VL. Immunology of leprosy and diagnostic challenges. Clin Dermatol. 2015;33: 90–98. doi:10.1016/j.clindermatol.2014.07.005spa
dc.relation.referencesCho SN, Yanagihara DL, Hunter SW, Gelber RH, Brennan PJ. Serological specificity of phenolic glycolipid I from Mycobacterium leprae and use in serodiagnosis of leprosy. Infect Immun. 1983;41: 1077–1083.spa
dc.relation.referencesHess S, Rambukkana A. Cell Biology of Intracellular Adaptation of Mycobacterium leprae in the Peripheral Nervous System. Microbiology Spectrum. 2019;7. doi:10.1128/microbiolspec.BAI-0020- 2019spa
dc.relation.referencesGaschignard J, Grant AV, Thuc NV, Orlova M, Cobat A, Huong NT, et al. Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases. PLOS Neglected Tropical Diseases. 2016;10: e0004345. doi:10.1371/journal.pntd.0004345spa
dc.relation.referencesNunzi E, Massone C, Noto S. Clinical Features. In: Nunzi E, Massone C, editors. Leprosy. Springer Milan; 2012. pp. 75–110. doi:10.1007/978-88-470-2376-5_10spa
dc.relation.referencesDaffé M, Draper P. The Envelope Layers of Mycobacteria with Reference to their Pathogenicity. In: Poole RK, editor. Advances in Microbial Physiology. Academic Press; 1997. pp. 131–203. doi:10.1016/S0065-2911(08)60016-8spa
dc.relation.referencesVissa VD, Brennan PJ. The genome of Mycobacterium leprae: a minimal mycobacterial gene set. Genome Biol. 2001;2: REVIEWS1023–REVIEWS1023. doi:10.1186/gb-2001-2-8-reviews1023spa
dc.relation.referencesChavarro-Portillo B, Colorado CL, Guerrero MI. Mycobacterium leprae. En: Guerrero MI, Hernández CA y Rodríguez G Editores La lepra: una enfermedad vigente Centro Dermatológico Federico Lleras Acosta Bogotá DC, Colombia Panamericana Formas e Impresos. Bogotá DC, Colombia; 2019. pp. 63–87.spa
dc.relation.referencesLiu J, Barry C, Besra G, Nikaido H. Mycolic acid structure determines the fluidity of the mycobacterial cell wall. The Journal of biological chemistry. 1996;271: 29545–29551. doi:10.1074/jbc.271.47.29545spa
dc.relation.referencesBrennan PJ, Nikaido H. THE ENVELOPE OF MYCOBACTERIA. Annu Rev Biochem. 1995;64: 29– 63. doi:10.1146/annurev.bi.64.070195.000333spa
dc.relation.referencesRambukkana A, Yamada H, Zanazzi G, Mathus T, Salzer JL, Yurchenco PD, et al. Role of alpha- dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science. 1998;282: 2076–9.spa
dc.relation.referencesNg V, Zanazzi G, Timpl R, Talts JF, Salzer JL, Brennan PJ, et al. Role of the Cell Wall Phenolic Glycolipid-1 in the Peripheral Nerve Predilection of Mycobacterium leprae. Cell. 2000;103: 511–524. doi:10.1016/S0092-8674(00)00142-2spa
dc.relation.referencesChang K-J, Redmond SA, Chan JR. Remodeling myelination: implications for mechanisms of neural plasticity. Nature Neuroscience. 2016;19: 190. doi:10.1038/nn.4200spa
dc.relation.referencesSpencer JS, Brennan PJ. The role of Mycobacterium leprae phenolic glycolipid I (PGL-I) in serodiagnosis and in the pathogenesis of leprosy. Leprosy review. 2011;82: 344–57.spa
dc.relation.referencesHunter SW, Brennan PJ. A novel phenolic glycolipid from Mycobacterium leprae possibly involved in immunogenicity and pathogenicity. Journal of bacteriology. 1981;147: 728–35.spa
dc.relation.referencesHunter SW, Fujiwara T, Brennan PJ. Structure and antigenicity of the major specific glycolipid antigen of Mycobacterium leprae. The Journal of biological chemistry. 1982;257: 15072–8.spa
dc.relation.referencesDíaz Acosta CC, Dias AA, Rosa TLSA, Batista-Silva LR, Rosa PS, Toledo-Pinto TG, et al. PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves. PLoS pathogens. 2018;14: e1007151–e1007151. doi:10.1371/journal.ppat.1007151spa
dc.relation.referencesRambukkana A, Zanazzi G, Tapinos N, Salzer JL. Contact-Dependent Demyelination by Mycobacterium leprae in the Absence of Immune Cells. Science. 2002;296: 927. doi:10.1126/science.1067631spa
dc.relation.referencesRambukkana A. How does Mycobacterium leprae target the peripheral nervous system? Trends in Microbiology. 2000;8: 23–28. doi:10.1016/S0966-842X(99)01647-9spa
dc.relation.referencesRambukkana A. Molecular basis for the peripheral nerve predilection of Mycobacterium leprae. Current Opinion in Microbiology. 2001;4: 21–27. doi:10.1016/S1369-5274(00)00159-4spa
dc.relation.referencesShimoji Y, Ng V, Matsumura K, Fischetti VA, Rambukkana A. A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion. Proceedings of the National Academy of Sciences of the United States of America. 1999;96: 9857–62.spa
dc.relation.referencesSmith WC, Aerts A. Role of contact tracing and prevention strategies in the interruption of leprosy transmission. Leprosy review. 2014;85: 2–17.spa
dc.relation.referencesWHO. Drug resistance in leprosy: reports from selected endemic countries. Weekly epidemiological record. 2009;84: 264–7.spa
dc.relation.referencesGonçalves FG, Belone A de FF, Rosa PS, Laporta GZ. Underlying mechanisms of leprosy recurrence in the Western Amazon: a retrospective cohort study. BMC Infect Dis. 2019;19: 460–460. doi:10.1186/s12879-019-4100-6spa
dc.relation.referencesGuerrero-Guerrero MI, Muvdi-Arenas S, Leon-Franco CI. Relapses in multibacillary leprosy patients: a retrospective cohort of 11 years in Colombia. Leprosy review. 2012;83: 247–60.spa
dc.relation.referencesda Silva Rocha A, Cunha Dos Santos AA, Pignataro P, Nery JA, de Miranda AB, Soares DF, et al. Genotyping of Mycobacterium leprae from Brazilian leprosy patients suggests the occurrence of reinfection or of bacterial population shift during disease relapse. J Med Microbiol. 2011;60: 1441–1446. doi:10.1099/jmm.0.029389-0spa
dc.relation.referencesWHO. Global leprosy: update on the 2012 situation. Weekly epidemiological record. 2013;88: 365–79.spa
dc.relation.referencesWHO. Global leprosy update, 2013; reducing disease burden. Weekly epidemiological record. 2014;89: 389–400.spa
dc.relation.referencesWHO. Global leprosy update, 2014: need for early case detection. Weekly epidemiological record. 2015;36 (99): 461–476.spa
dc.relation.referencesWHO. Global leprosy update, 2015: time for action, accountability and inclusion. Weekly epidemiological record. 2016;35: 405–420.spa
dc.relation.referencesWHO. Global leprosy (Hansen disease) update, 2019: time to step-up prevention initiatives. Weekly Epidemiological Record. 4 Sep 202095: 417–440.spa
dc.relation.referencesAli MK, Thorat DM, Subramanian M, Parthasarathy G, Selvaraj U, Prabhakar V. A study on trend of relapse in leprosy and factors influencing relapse. Indian journal of leprosy. 2005;77: 105–15.spa
dc.relation.referencesShen J, Liu M, Zhang J, Su W, Ding G. Relapse in MB leprosy patients treated with 24 months of MDT in south west China: a short report. Leprosy review. 2006;77: 219–24.spa
dc.relation.referencesFerreira SMB, Ignotti E, Senigalia LM, Silva DRX, Gamba MA. Recidivas de casos de hanseníase no estado de Mato Grosso. Revista de Saúde Pública. 2010;44: 650–657spa
dc.relation.referencesWHO. Global leprosy situation, 2010. Weekly epidemiological record. 2010;85(35): 337–48.spa
dc.relation.referencesGuerrero MI Colorado, C, Muvdi, S, Leon-Franco, CI,. Informe final estudio de recaídas en pacientes con lepra multibacilar, experiencia del Centro Dermatologico Federico Lleras Acosta-E.S.E Bogotá, Colombia. Fase 2. 2010.spa
dc.relation.referencesMonot M, Honoré N, Balière C, Ji B, Sow S, Brennan PJ, et al. Are Variable-Number Tandem Repeats Appropriate for Genotyping Mycobacterium leprae? Journal of clinical microbiology. 2008;46: 2291. doi:10.1128/jcm.00239-08spa
dc.relation.referencesStefani MMA, Avanzi C, Bührer-Sékula S, Benjak A, Loiseau C, Singh P, et al. Whole genome sequencing distinguishes between relapse and reinfection in recurrent leprosy cases. PLOS Neglected Tropical Diseases. 2017;11: e0005598. doi:10.1371/journal.pntd.0005598spa
dc.relation.referencesSmith CS, Noordeen SK, Richardus JH, Sansarricq H, Cole ST, Soares RC, et al. A strategy to halt leprosy transmission. The Lancet infectious diseases. 2014;14: 96–8. doi:10.1016/S1473- 3099(13)70365-7spa
dc.relation.referencesMoet FJ, Pahan D, Schuring RP, Oskam L, Richardus JH. Physical distance, genetic relationship, age, and leprosy classification are independent risk factors for leprosy in contacts of patients with leprosy. The Journal of infectious diseases. 2006;193: 346–53. doi:10.1086/499278spa
dc.relation.referencesFischer E, De Vlas S, Meima A, Habbema D, Richardus J. Different mechanisms for heterogeneity in leprosy susceptibility can explain disease clustering within households. PloS one. 2010;5: e14061. doi:10.1371/journal.pone.0014061spa
dc.relation.referencesAl Awaidy ST. Progress towards a leprosy-free country: The experience of Oman. PLOS Neglected Tropical Diseases. 2017;11: e0006028. doi:10.1371/journal.pntd.0006028spa
dc.relation.referencesMaiden MCJ. Putting leprosy on the map. Nature Genetics. 2009;41: 1264. doi:10.1038/ng1209- 1264spa
dc.relation.referencesWHO. Model Prescribing Information: Drugs Used in Leprosy. 1998. Available: http://apps.who.int/medicinedocs/en/m/abstract/Js23543en/spa
dc.relation.referencesWHO. Multidrug therapy (MDT). In: WHO [Internet]. [cited 9 Feb 2020]. Available: http://www.who.int/lep/mdt/en/spa
dc.relation.referencesWHO. WHO Expert Committee on Leprosy. World Health Organization technical report series. 2012;968: 1–61.spa
dc.relation.referencesGirdhar BK., Girdhar A., A. K. Relapses in multibacillary leprosy patients: effect of length of therapy. Lepr Rev. 2000;71: 144–53.spa
dc.relation.referencesGirdhar BK, Girdhar A, Kumar A. Relapses in multibacillary leprosy patients: effect of length of therapy. Leprosy review. 2000;71: 144–53.spa
dc.relation.referencesGuerrero MI, Colorado CL, Torres JF, León CI. Is drug-resistant Mycobacterium leprae a real cause for concern?: First approach to molecular monitoring of multibacillary Colombian patients with and without previous leprosy treatment. Biomédica. 2014;34: 137–147.spa
dc.relation.referencesNational JALMA Institute of Leprosy and Other Mycobacterial Diseases. Informal consultation on rifampicin resistance in leprosy. Lepr Rev. 2007;3: 295–305. doi:10.47276/lr.78.3.295spa
dc.relation.referencesMeyer M, Kircher M. Illumina Sequencing Library Preparation for Highly Multiplexed Target Capture and Sequencing. Cold Spring Harbor Protocols. 2010;2010: pdb.prot5448. doi:10.1101/pdb.prot5448spa
dc.relation.referencesPeltzer A, Jäger G, Herbig A, Seitz A, Kniep C, Krause J, et al. EAGER: efficient ancient genome reconstruction. Genome Biol. 2016;17: 60–60. doi:10.1186/s13059-016-0918-zspa
dc.relation.referencesLangmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nature Methods. 2012;9: 357–359. doi:10.1038/nmeth.1923spa
dc.relation.referencesJónsson H, Ginolhac A, Schubert M, Johnson PLF, Orlando L. mapDamage2.0: fast approximate Bayesian estimates of ancient DNA damage parameters. Bioinformatics. 2013;29: 1682–1684. doi:10.1093/bioinformatics/btt193spa
dc.relation.referencesMcKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20: 1297–1303. doi:10.1101/gr.107524.110spa
dc.relation.referencesCingolani P, Platts A, Wang LL, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 2012;6: 80–92. doi:10.4161/fly.19695spa
dc.relation.referencesLi H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics (Oxford, England). 2009;25: 2078–2079. doi:10.1093/bioinformatics/btp352spa
dc.relation.referencesKoboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD, Lin L, et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 2012/02/02 ed. 2012;22: 568–576. doi:10.1101/gr.129684.111spa
dc.relation.referencesDanecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011/06/07 ed. 2011;27: 2156–2158. doi:10.1093/bioinformatics/btr330spa
dc.relation.referencesHuerta-Cepas J, Szklarczyk D, Heller D, Hernández-Plaza A, Forslund SK, Cook H, et al. eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses. Nucleic Acids Research. 2019;47: D309–D314. doi:10.1093/nar/gky1085spa
dc.relation.referencesBankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, et al. SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing. Journal of Computational Biology. 2012;19: 455–477. doi:10.1089/cmb.2012.0021spa
dc.relation.referencesSuchard MA, Lemey P, Baele G, Ayres DL, Drummond AJ, Rambaut A. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10. Virus Evolution. 2018;4. doi:10.1093/ve/vey016spa
dc.relation.referencesRambaut A, Drummond AJ, Xie D, Baele G, Suchard MA. Posterior Summarization in Bayesian Phylogenetics Using Tracer 1.7. Systematic Biology. 2018;67: 901–904. doi:10.1093/sysbio/syy032spa
dc.relation.referencesRambaut A, Lam TT, Max Carvalho L, Pybus OG. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evol. 2016;2: vew007–vew007. doi:10.1093/ve/vew007spa
dc.relation.referencesKumar S, Stecher G, Li M, Knyaz C, Tamura K. MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Molecular Biology and Evolution. 2018;35: 1547–1549. doi:10.1093/molbev/msy096spa
dc.relation.referencesRobinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES, Getz G, et al. Integrative genomics viewer. Nature Biotechnology. 2011;29: 24–26. doi:10.1038/nbt.1754spa
dc.relation.referencesBryant JM, Harris SR, Parkhill J, Dawson R, Diacon AH, van Helden P, et al. Whole-genome sequencing to establish relapse or re-infection with Mycobacterium tuberculosis: a retrospective observational study. Lancet Respir Med. 2013/11/21 ed. 2013;1: 786–792. doi:10.1016/S2213- 2600(13)70231-5spa
dc.relation.referencesWitney AA, Bateson ALE, Jindani A, Phillips PPJ, Coleman D, Stoker NG, et al. Use of whole- genome sequencing to distinguish relapse from reinfection in a completed tuberculosis clinical trial. BMC Med. 2017;15: 71–71. doi:10.1186/s12916-017-0834-4spa
dc.relation.referencesDarling AE, Mau B, Perna NT. progressiveMauve: multiple genome alignment with gene gain, loss and rearrangement. PloS one. 2010;5: e11147. doi:10.1371/journal.pone.0011147spa
dc.relation.referencesGröschel MI, Sayes F, Simeone R, Majlessi L, Brosch R. ESX secretion systems: mycobacterial evolution to counter host immunity. Nature Reviews Microbiology. 2016;14: 677–691. doi:10.1038/nrmicro.2016.131spa
dc.relation.referencesDaffe M, Crick DC, Jackson M. Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids. Microbiology spectrum. 2014;2: MGM2-0021–2013. doi:10.1128/microbiolspec.MGM2- 0021-2013spa
dc.relation.referencesPallen MJ. The ESAT-6/WXG100 superfamily – and a new Gram-positive secretion system? Trends in Microbiology. 2002;10: 209–212. doi:10.1016/S0966-842X(02)02345-4spa
dc.relation.referencesTufariello JM, Chapman JR, Kerantzas CA, Wong K-W, Vilchèze C, Jones CM, et al. Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence. Proc Natl Acad Sci USA. 2016;113: E348. doi:10.1073/pnas.1523321113spa
dc.relation.referencesLockwood DNJ, Suneetha S. Leprosy: too complex a disease for a simple elimination paradigm. Bull World Health Organ. 2005/03/16 ed. 2005;83: 230–235.spa
dc.relation.referencesWHO Technical Advisory Group on Elimination of Leprosy. Meeting (3rd: 2002: Brasilia B, World Health Organization. Strategy Development and Monitoring for Eradication and Elimination Team, Leprosy Elimination Advisory Group. Meeting. Report on third meeting of the WHO Technical Advisory Group on Elimination of Leprosy, Brasilia, 1 and 2 February 2002. Rapport de la troisième réunion du groupe consultatif technique de l’OMS sur l’élimination de la lèpre, Brasilia, 1 et 2 février 2002. 2002. Available: https://apps.who.int/iris/handle/10665/67302spa
dc.relation.referencesScollard DM. Leprosy treatment: Can we replace opinions with research? PLOS Neglected Tropical Diseases. 2020;14: e0008636. doi:10.1371/journal.pntd.0008636spa
dc.relation.referencesBalagon MF, Cellona RV, Cruz E dela, Burgos JA, Abalos RM, Walsh GP, et al. Long-Term Relapse Risk of Multibacillary Leprosy after Completion of 2 Years of Multiple Drug Therapy (WHO-MDT) in Cebu, Philippines. The American Journal of Tropical Medicine and Hygiene Am J Trop Med Hyg. 2009;81: 895–899. doi:10.4269/ajtmh.2009.09-0189spa
dc.relation.referencesNorman G, Joseph G, Richard J. Relapses in multibacillary patients treated with multi-drug therapy until smear negativity: findings after twenty years. International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association. 2004;72: 1–7. doi:10.1489/1544-581X(2004)072<0001:RIMPTW>2.0.CO;2spa
dc.relation.referencesWalker TM, Ip CLC, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis. 2013;13: 137–146. doi:10.1016/s1473-3099(12)70277-3spa
dc.relation.referencesBryant JM, Schürch AC, van Deutekom H, Harris SR, de Beer JL, de Jager V, et al. Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data. BMC Infect Dis. 2013;13: 110–110. doi:10.1186/1471-2334-13-110spa
dc.relation.referencesPérez-Lago L, Comas I, Navarro Y, González-Candelas F, Herranz M, Bouza E, et al. Whole Genome Sequencing Analysis of Intrapatient Microevolution in Mycobacterium tuberculosis: Potential Impact on the Inference of Tuberculosis Transmission. The Journal of Infectious Diseases. 2014;209: 98–108. doi:10.1093/infdis/jit439spa
dc.relation.referencesAvanzi C, Lécorché E, Rakotomalala FA, Benjak A, Rapelanoro Rabenja F, Ramarozatovo LS, et al. Population Genomics of Mycobacterium leprae Reveals a New Genotype in Madagascar and the Comoros. Frontiers in Microbiology. 2020;11: 711. doi:10.3389/fmicb.2020.00711spa
dc.relation.referencesCardona-Castro N, Cortés E, Beltrán C, Romero M, Badel-Mogollón JE, Bedoya G. Human Genetic Ancestral Composition Correlates with the Origin of Mycobacterium leprae Strains in a Leprosy Endemic Population. PLoS Negl Trop Dis. 2015;9: e0004045. doi:10.1371/journal.pntd.0004045spa
dc.relation.referencesSharma R, Singh P, Pena M, Subramanian R, Chouljenko V, Kim J, et al. Differential growth of Mycobacterium leprae strains (SNP genotypes) in armadillos. Infection, Genetics and Evolution. 2018;62: 20–26. doi:10.1016/j.meegid.2018.04.017spa
dc.relation.referencesUplekar S, Heym B, Friocourt V, Rougemont J, Cole ST. Comparative genomics of Esx genes from clinical isolates of Mycobacterium tuberculosis provides evidence for gene conversion and epitope variation. Infect Immun. 2011/08/01 ed. 2011;79: 4042–4049. doi:10.1128/IAI.05344-11spa
dc.relation.referencesGeluk A, Van Meijgaarden KE, Franken KLMC, Wieles B, Arend SM, Faber WR, et al. Immunological Crossreactivity of the Mycobacterium leprae CFP-10 with its Homologue in Mycobacterium tuberculosis. Scandinavian Journal of Immunology. 2004;59: 66–70. doi:10.1111/j.0300- 9475.2004.01358.xspa
dc.relation.referencesGeluk A, van Meijgaarden KE, Franken KLMC, Subronto YW, Wieles B, Arend SM, et al. Identification and Characterization of the ESAT-6 Homologue of Mycobacterium leprae and T-Cell Cross- Reactivity with Mycobacterium tuberculosis. Infect Immun. 2002;70: 2544. doi:10.1128/IAI.70.5.2544- 2548.2002spa
dc.relation.referencesMostowy S, Cossart P. From Pathogenesis to Cell Biology and Back. Cell Host & Microbe. 2009;5: 510–513. doi:10.1016/j.chom.2009.06.002spa
dc.relation.referencesGurdon JB, Melton DA. Nuclear Reprogramming in Cells. Science. 2008;322: 1811. doi:10.1126/science.1160810spa
dc.relation.referencesTheise ND, Wilmut I. Cell plasticity: Flexible arrangement. Nature. 2003;425: 21–21. doi:10.1038/425021aspa
dc.relation.referencesFalkow S. Bacterial entry into eukaryotic cells. Cell. 1991;65: 1099–1102. doi:10.1016/0092- 8674(91)90003-hspa
dc.relation.referencesKim HA, Mindos T, Parkinson DB. Plastic fantastic: Schwann cells and repair of the peripheral nervous system. Stem cells translational medicine. 2013;2: 553–557. doi:10.5966/sctm.2013-0011spa
dc.relation.referencesJessen KR, Mirsky R. The origin and development of glial cells in peripheral nerves. Nature Reviews Neuroscience. 2005;6: 671–682. doi:10.1038/nrn1746spa
dc.relation.referencesRambukkana A. Mycobacterium leprae-induced demyelination: a model for early nerve degeneration. Current Opinion in Immunology. 2004;16: 511–518. doi:10.1016/j.coi.2004.05.021spa
dc.relation.referencesJessen KR, Mirsky R. Negative regulation of myelination: Relevance for development, injury, and demyelinating disease. Glia. 2008;56: 1552–1565. doi:10.1002/glia.20761spa
dc.relation.referencesChen Z-L, Yu W-M, Strickland S. Peripheral Regeneration. Annu Rev Neurosci. 2007;30: 209– 233. doi:10.1146/annurev.neuro.30.051606.094337spa
dc.relation.referencesRambukkana A. Usage of signaling in neurodegeneration and regeneration of peripheral nerves by leprosy bacteria. Progress in Neurobiology. 2010;91: 102–107. doi:10.1016/j.pneurobio.2009.12.002spa
dc.relation.referencesHess S, Rambukkana A. Bacterial-induced cell reprogramming to stem cell-like cells: new premise in host–pathogen interactions. Current Opinion in Microbiology. 2015;23: 179–188. doi:10.1016/j.mib.2014.11.021spa
dc.relation.referencesRambukkana A, Salzer JL, Yurchenco PD, Tuomanen EI. Neural Targeting of Mycobacterium leprae Mediated by the G Domain of the Laminin-α2 Chain. Cell. 1997;88: 811–821. doi:10.1016/S0092- 8674(00)81927-3spa
dc.relation.referencesToshihiro M, Aidan M, Justyna C-W, Jinrong Q, R. TS, Anura R. Innate Immune Response Precedes Mycobacterium leprae–Induced Reprogramming of Adult Schwann Cells. Cellular Reprogramming. 2014;16: 9–17. doi:10.1089/cell.2013.0064spa
dc.relation.referencesMasaki T, McGlinchey A, Tomlinson SR, Qu J, Rambukkana A. Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts. F1000Res. 2013;2: 198–198. doi:10.12688/f1000research.2-198.v3spa
dc.relation.referencesSmith CS, Aerts A, Saunderson P, Kawuma J, Kita E, Virmond M. Multidrug therapy for leprosy: a game changer on the path to elimination. Lancet Infect Dis. 2017;17: e293–e297. doi:10.1016/S1473- 3099(17)30418-8spa
dc.relation.referencesSharma R, Lahiri R, Scollard DM, Pena M, Williams DL, Adams LB, et al. The armadillo: a model for the neuropathy of leprosy and potentially other neurodegenerative diseases. Dis Model Mech. 2012/12/05 ed. 2013;6: 19–24. doi:10.1242/dmm.010215spa
dc.relation.referencesTruman RW, Ebenezer GJ, Pena MT, Sharma R, Balamayooran G, Gillingwater TH, et al. The Armadillo as a Model for Peripheral Neuropathy in Leprosy. ILAR Journal. 2014;54: 304–314. doi:10.1093/ilar/ilt050spa
dc.relation.referencesMuñetón-Gómez VC. Use of Schwann cell cultures in the study of Mycobacterium leprae in vitro infection. Pontificia Universidad Javeriana. 1996.spa
dc.relation.referencesHagge DA, Oby Robinson S, Scollard D, McCormick G, Williams DL. A New Model for Studying the Effects of Mycobacterium leprae on Schwann Cell and Neuron Interactions. J Infect Dis. 2002;186: 1283–1296. doi:10.1086/344313spa
dc.relation.referencesMiko TL, Le Maitre C, Kinfu Y. Damage and regeneration of peripheral nerves in advanced treated leprosy. The Lancet. 1993;342: 521–525. doi:10.1016/0140-6736(93)91647-5spa
dc.relation.referencesArbues A, Lugo-Villarino G, Neyrolles O, Guilhot C, Astarie-Dequeker C. Playing hide-and-seek with host macrophages through the use of mycobacterial cell envelope phthiocerol dimycocerosates and phenolic glycolipids. Front Cell Infect Microbiol. 2014;4: 173–173. doi:10.3389/fcimb.2014.00173spa
dc.relation.referencesGuenin-Macé L, Siméone R, Demangel C. Lipids of Pathogenic Mycobacteria: Contributions to Virulence and Host Immune Suppression. Transboundary and Emerging Diseases. 2009;56: 255–268. doi:10.1111/j.1865-1682.2009.01072.xspa
dc.relation.referencesDaffé M, Laneelle MA. Distribution of Phthiocerol Diester, Phenolic Mycosides and Related Compounds in Mycobacteria. Microbiology. Microbiology Society; 1988. pp. 2049–2055. doi:https://doi.org/10.1099/00221287-134-7-2049spa
dc.relation.referencesTabouret G, Astarie-Dequeker C, Demangel C, Malaga W, Constant P, Ray A, et al. Mycobacterium leprae Phenolglycolipid-1 Expressed by Engineered M. bovis BCG Modulates Early Interaction with Human Phagocytes. PLoS Pathogens. 2010;6: e1001159. doi:10.1371/journal.ppat.1001159spa
dc.relation.referencesPérez E, Constant P, Lemassu A, Laval F, Daffé M, Guilhot C. Characterization of Three Glycosyltransferases Involved in the Biosynthesis of the Phenolic Glycolipid Antigens from the Mycobacterium tuberculosis Complex. Journal of Biological Chemistry. 2004;279: 42574–42583. doi:10.1074/jbc.M406246200spa
dc.relation.referencesPérez E, Constant P, Laval F, Lemassu A, Lanéelle M-A, Daffé M, et al. Molecular Dissection of the Role of Two Methyltransferases in the Biosynthesis of Phenolglycolipids and Phthiocerol Dimycoserosate in the Mycobacterium tuberculosis Complex *. Journal of Biological Chemistry. 2004;279: 42584–42592. doi:10.1074/jbc.M406134200spa
dc.relation.referencesOnwueme KC, Vos CJ, Zurita J, Ferreras JA, Quadri LEN. The dimycocerosate ester polyketide virulence factors of mycobacteria. Progress in Lipid Research. 2005;44: 259–302. doi:10.1016/j.plipres.2005.07.001spa
dc.relation.referencesAzad AK, Sirakova TD, Fernandes ND, Kolattukudy PE. Gene Knockout Reveals a Novel Gene Cluster for the Synthesis of a Class of Cell Wall Lipids Unique to Pathogenic Mycobacteria *. Journal of Biological Chemistry. 1997;272: 16741–16745. doi:10.1074/jbc.272.27.16741spa
dc.relation.referencesLove MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15: 550–550. doi:10.1186/s13059-014-0550-8spa
dc.relation.referencesLangfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9: 559–559. doi:10.1186/1471-2105-9-559spa
dc.relation.referencesKapopoulou A, Lew JM, Cole ST. The MycoBrowser portal: A comprehensive and manually annotated resource for mycobacterial genomes. Tuberculosis. 2011;91: 8–13. doi:10.1016/j.tube.2010.09.006spa
dc.relation.referencesYe J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13: 134–134. doi:10.1186/1471-2105-13-134spa
dc.relation.referencesUntergasser A, Nijveen H, Rao X, Bisseling T, Geurts R, Leunissen JAM. Primer3Plus, an enhanced web interface to Primer3. Nucleic Acids Res. 2007/05/07 ed. 2007;35: W71–W74. doi:10.1093/nar/gkm306spa
dc.relation.referencesThornton B, Basu C. Real-time PCR (qPCR) primer design using free online software. Biochemistry and Molecular Biology Education. 2011;39: 145–154. doi:10.1002/bmb.20461spa
dc.relation.referencesLivak KJ, Schmittgen TD. Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method. Methods. 2001;25: 402–408. doi:10.1006/meth.2001.1262spa
dc.relation.referencesEwels 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/btw354spa
dc.relation.referencesBolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30: 2114–20. doi:10.1093/bioinformatics/btu170spa
dc.relation.referencesHumphrys MS, Creasy T, Sun Y, Shetty AC, Chibucos MC, Drabek EF, et al. Simultaneous Transcriptional Profiling of Bacteria and Their Host Cells. PLOS ONE. 2013;8: e80597. doi:10.1371/journal.pone.0080597spa
dc.relation.referencesAsai S, Rallapalli G, Piquerez SJM, Caillaud M-C, Furzer OJ, Ishaque N, et al. Expression Profiling during Arabidopsis/Downy Mildew Interaction Reveals a Highly-Expressed Effector That Attenuates Responses to Salicylic Acid. PLOS Pathogens. 2014;10: e1004443. doi:10.1371/journal.ppat.1004443spa
dc.relation.referencesSocquet-Juglard D, Kamber T, Pothier JF, Christen D, Gessler C, Duffy B, et al. Comparative RNA- Seq Analysis of Early-Infected Peach Leaves by the Invasive Phytopathogen Xanthomonas arboricola pv. pruni. PLOS ONE. 2013;8: e54196. doi:10.1371/journal.pone.0054196spa
dc.relation.referencesAbdallah AM, Weerdenburg EM, Guan Q, Ummels R, Borggreve S, Adroub SA, et al. Integrated transcriptomic and proteomic analysis of pathogenic mycobacteria and their esx-1 mutants reveal secretion-dependent regulation of ESX-1 substrates and WhiB6 as a transcriptional regulator. PLoS One. 2019;14: e0211003–e0211003. doi:10.1371/journal.pone.0211003spa
dc.relation.referencesRechavi O, Kalman M, Fang Y, Vernitsky H, Jacob-Hirsch J, Foster LJ, et al. Trans-SILAC: sorting out the non-cell-autonomous proteome. Nature Methods. 2010;7: 923–927. doi:10.1038/nmeth.1513spa
dc.relation.referencesPapenfort K, Vogel J. Regulatory RNA in Bacterial Pathogens. Cell Host & Microbe. 2010;8: 116– 127. doi:10.1016/j.chom.2010.06.008spa
dc.relation.referencesWestermann AJ, Gorski SA, Vogel J. Dual RNA-seq of pathogen and host. Nature Reviews Microbiology. 2012;10: 618–630. doi:10.1038/nrmicro2852spa
dc.relation.referencesWilliams DL, Torrero M, Wheeler PR, Truman RW, Yoder M, Morrison N, et al. Biological Implications of Mycobacterium leprae Gene Expression during Infection. Journal of Molecular Microbiology and Biotechnology. 2004;8: 58–72. doi:10.1159/000082081spa
dc.relation.referencesKawahara Y, Oono Y, Kanamori H, Matsumoto T, Itoh T, Minami E. Simultaneous RNA-Seq Analysis of a Mixed Transcriptome of Rice and Blast Fungus Interaction. PLOS ONE. 2012;7: e49423. doi:10.1371/journal.pone.0049423spa
dc.relation.referencesYazawa T, Kawahigashi H, Matsumoto T, Mizuno H. Simultaneous Transcriptome Analysis of Sorghum and Bipolaris sorghicola by Using RNA-seq in Combination with De Novo Transcriptome Assembly. PLOS ONE. 2013;8: e62460. doi:10.1371/journal.pone.0062460spa
dc.relation.referencesPetre B, Morin E, Tisserant E, Hacquard S, Da Silva C, Poulain J, et al. RNA-Seq of Early-Infected Poplar Leaves by the Rust Pathogen Melampsora larici-populina Uncovers PtSultr3;5, a Fungal-Induced Host Sulfate Transporter. PLOS ONE. 2012;7: e44408. doi:10.1371/journal.pone.0044408spa
dc.relation.referencesMontoya DJ, Andrade P, Silva BJA, Teles RMB, Ma F, Bryson B, et al. Dual RNA-Seq of Human Leprosy Lesions Identifies Bacterial Determinants Linked to Host Immune Response. Cell Reports. 2019;26: 3574-3585.e3. doi:10.1016/j.celrep.2019.02.109spa
dc.relation.referencesBitter W, Houben ENG, Bottai D, Brodin P, Brown EJ, Cox JS, et al. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog. 2009/10/30 ed. 2009;5: e1000507– e1000507. doi:10.1371/journal.ppat.1000507spa
dc.relation.referencesMacGurn JA, Cox JS. A genetic screen for Mycobacterium tuberculosis mutants defective for phagosome maturation arrest identifies components of the ESX-1 secretion system. Infect Immun. 2007/03/12 ed. 2007;75: 2668–2678. doi:10.1128/IAI.01872-06spa
dc.relation.referencesChampion MM, Williams EA, Pinapati RS, Champion PAD. Correlation of phenotypic profiles using targeted proteomics identifies mycobacterial esx-1 substrates. J Proteome Res. 2014/08/25 ed. 2014;13: 5151–5164. doi:10.1021/pr500484wspa
dc.relation.referencesLee Y, Colston MJ. Measurement of ATP generation and decay in Mycobacterium leprae in vitro 1985. J Gen Microbiol. 1985;12: 3331–7. doi:10.1099/00221287-131-12-3331. PMID: 3913745.spa
dc.relation.referencesNandi SK, Chakraborty A, Panda AK, Ray SS, Kar RK, Bhunia A, et al. Interaction of ATP with a small heat shock protein from Mycobacterium leprae: effect on its structure and function. PLoS neglected tropical diseases. 2015;9: e0003661. doi:10.1371/journal.pntd.0003661spa
dc.relation.referencesAvanzi C, Busso P, Benjak A, Loiseau C, Fomba A, Doumbia G, et al. Transmission of Drug- Resistant Leprosy in Guinea-Conakry Detected Using Molecular Epidemiological Approaches. Clinical Infectious Diseases. 2016;63: 1482–1484. doi:10.1093/cid/ciw572spa
dc.relation.referencesOliveira MBB de, Diniz LM. Leprosy among children under 15 years of age: literature review. An Bras Dermatol. 2016;91: 196–203. doi:10.1590/abd1806-4841.20163661spa
dc.relation.referencesMendum TA, Schuenemann VJ, Roffey S, Taylor GM, Wu H, Singh P, et al. Mycobacterium leprae genomes from a British medieval leprosy hospital: towards understanding an ancient epidemic. BMC Genomics. 2014;15: 270. doi:10.1186/1471-2164-15-270spa
dc.relation.referencesHonoré N, Perrani E, Telenti A, Grosset J, Cole S. A simple and rapid technique for the detection of rifampin resistance in Mycobacterium leprae. International journal of leprosy and other mycobacterial diseases: official organ of the International Leprosy Association. 1993;61: 600–604.spa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.ddc610 - Medicina y saludspa
dc.subject.decsRecurrenciaspa
dc.subject.decsRecurrenceeng
dc.subject.decsMycobacterium lepraespa
dc.subject.decsMycobacterium lepraeeng
dc.subject.proposalGenotipospa
dc.subject.proposalCélulas de Schwanneng
dc.subject.proposalRecaídaeng
dc.subject.proposalReinfecciónspa
dc.subject.proposalGenotypeeng
dc.subject.proposalSchwann Cellseng
dc.subject.proposalRelapseeng
dc.subject.proposalReinfectioneng
dc.titleEstudio de cepas de Mycobacterium leprae colombiano causantes de múltiples episodios sintomáticos de lepra post poliquimioterapiaspa
dc.title.translatedStudy of Colombian strains of Mycobacterium leprae causing multiple symptomatic episodes of post-polychemotherapy leprosyeng
dc.typeTrabajo de grado - Doctoradospa
dc.type.coarhttp://purl.org/coar/resource_type/c_db06spa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/doctoralThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TDspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentGrupos comunitariosspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa
oaire.awardtitleConvocatoria de Doctorados Nacionales 727 - 2015spa
oaire.fundernameMinisterio de Ciencia y Tecnologiaspa

Archivos

Bloque original

Mostrando 1 - 1 de 1
Miniatura
Nombre:
53133739.2021.pdf
Tamaño:
3.35 MB
Formato:
Adobe Portable Document Format
Descripción:
Tesis de Doctorado en Biotecnología
Descargar

Bloque de licencias

Mostrando 1 - 1 de 1
Miniatura
Nombre:
license.txt
Tamaño:
5.74 KB
Formato:
Item-specific license agreed upon to submission
Descripción:
Descargar

Colecciones

Doctorado en Biotecnología