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Susceptibilidad del huésped a las infecciones fúngicas invasoras
Se estima que más de un millón y medio de personas mueren al año en el mundo debido a una enfermedad fúngica invasora (EFI). Los tratamientos con inmunosupresores, terapias con corticoides, trasplantes de células hematopoyéticas y órgano sólido así como tratamientos quimioterapéuticos contra el cáncer han favorecido el aumento de estas infecciones fúngicas. El género Aspergillus es la principal causa de EFI por hongos filamentosos, siendo A. fumigatus la especie principalmente aislada en la mayoría de los casos y más frecuentemente asociada a Aspergilosis Invasora.
Muchas de estas infecciones están infra-diagnosticadas debido, tanto a la falta de sospecha clínica como a las limitaciones diagnósticas. Esta línea de investigación tiene como principal objetivo mejorar el pronóstico de la infecciones en pacientes con riesgo de desarrollar infecciones invasoras por hongos. Para ello se estudian marcadores del individuo (denominados biomarcadores del hospedador) que puedan ser detectados de forme temprana en muestras de pacientes en riesgo y que nos permita estratificar a los mismos en función de la susceptibilidad a desarrollar una infección invasora por hongos. Además, estudios realizados en los últimos años muestran que el fondo genético del hospedador está asociado con la predisposición al desarrollo de este tipo de enfermedades. En concreto se han identificado polimorfismos genéticos de nucleótido simple (“Single Nucleotide Polymorphism”- SNP) en genes que codifican para componentes celulares que interaccionan con estructuras fúngicas y/o que están involucradas en la respuesta inmune del huésped frente a agentes infecciosos como Aspergillus. En este sentido se han estandarizado y aplicado herramientas para la detección de SNPs en humanos de genes diana asociados concretamente con la susceptibilidad a la Aspergilosis Invasora.
Estudio de los mecanismos de virulencia en Aspergillus fumigatus
En paralelo al estudio de la respuesta del hospedador se sigue una línea cuyo objetivo es caracterizar mecanismos de virulencia en A. fumigatus. Uno de los principales mecanismos por los que A. fumigatus es capaz de causar enfermedad en humanos es su capacidad de adaptarse a las condiciones ambientales del hospedador. Entre las moléculas y los genes que se han relacionado con la virulencia de este hongo se encuentran componentes de la pared celular, genes y moléculas relacionadas con la evasión de la respuesta inmune, sistemas de detoxificación de los compuestos derivados del oxígeno, la producción de toxinas, la obtención de nutrientes como hierro, fósforo, nitrógeno y la adaptación a pH y temperatura del hospedador. Estos estudios permiten profundizar en el conocimiento sobre la patogenicidad de este hongo e identificar nuevas dianas terapéuticas
Publications
Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin
Garcia-Barreno B, Delgado T, Benito S, Casas I, Pozo F, Cuevas MT, et al. Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin. J Gen Virol. 2014;95(Pt 5):1033-42.
PUBMED DOIEpidemic history of hepatitis C virus genotypes and subtypes in Portugal.
Palladino C, Ezeonwumelu IJ, Marcelino R, Briz V, Moranguinho I, Serejo F, Velosa JF, Tato Marinho R, Borrego P, Taveira N. 2018. Epidemic history of hepatitis C virus genotypes and subtypes in Portugal. Sci Rep. 2018; 8:12266. (A; FI= 4.12; Q1 Multidisciplinary Sciences; DOI:10.1038/s41598-018-30528-0).
PUBMED DOILow frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study.
Palladino C, Sanchez-Carrillo M, Mate-Cano I, Vazquez-Morón S, Jiménez-Sousa MA, Gutiérrez-Rivas M, Resino S, Briz V. Low frequency of NS5A relevant resistance-associated substitutions to Elbasvir among hepatitis C virus genotype 1a in Spain: a cross-sectional study. Sci Rep. 2017; 7(1):2892. (A; FI= 4.12; Q1 Multidisciplinary Sciences).
PUBMED DOIPlasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernández-Pato A; Virseda-Berdices A, Ryan P; Martínez-González O, Peréz-García F, Resino S, Martin-Vicente M, Valle-Millares D, Brochado-Kith O; Blancas R; Ceballos FC; Bartolome-Sánchez S; Vidal-Alcántara EJ; Alonso-Menchén D, Blanca-López N; Ramirez Martinez-Acitores I, Rava M, Jiménez-Sousa MA (‡ *), Amanda Fernández-Rodríguez (‡ *). Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. Emerg Microbes Infect 2022; 11(1):676-688 (A; FI= 19.57; D1, Infectious Diseases; JCR 2021).
PUBMED DOIMild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study.
García-Broncano P, Medrano LM, Berenguer J, Brochado O, González-García J, Jiménez-Sousa MA, Quereda C, Sanz J, Téllez MJ, Díaz L, Jiménez JL, Muñoz-Fernández MA, Resino S (*). Mild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study. J Infect 2020; 80(1):99-110. (A; FI= 6.07; Q1, Infectious Diseases; JCR 2020).
PUBMED DOIEfficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease
Buitrago MJ, Aguado JM, Ballen A, Bernal-Martinez L, Prieto M, Garcia-Reyne A, Garcia-Rodriguez J, Rodriguez-Tudela JL, Cuenca-Estrella M. Efficacy of DNA amplification in tissue biopsy samples to improve the detection of invasive fungal disease. Clin Microbiol Infect. 2013 Jun;19(6):E271-7. doi: 10.1111/1469-0691.12110. Epub 2013 Mar 7. PMID: 23464751.
PUBMED DOIPotent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses
Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V, Yuste E. J Virol. 2022 Jan 12, 96(1): e0134321
PUBMED DOIHIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic
Cabrera-Rodríguez R, Hebmann V, Marfil S, Pernas M, Marrero-Hernández S, Cabrera C, Urrea V, Casado C, Olivares I, Márquez-Arce D, Pérez-Yanes S, Estévez-Herrera J, Clotet B, Espert L, López-Galíndez C, Biard-Piechaczyk M, Valenzuela-Fernández A, Blanco J. Sci Rep. 2019 Apr 3,9(1):5544
PUBMED DOIViral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers
Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera MS, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C. mBio. 2018 Apr 10,9(2): e02338-17
PUBMED DOIViral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors.
Colomer-Lluch M, Kilpelainen A, Pernas M, Peña R, Ouchi D, Jimenez-Moyano E, Dalmau J, Casado C, López-Galíndez C, Clotet B, Martinez-Picado J, Prado JG. J Virol. 2022 Jan 12, 96(1): e0149921. doi: 10.1128/JVI.01499-21. Epub 2021 Oct 20.
PUBMED DOIContribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression
Valenzuela-Fernández A, Cabrera-Rodríguez R, Casado C, Pérez-Yanes S, Pernas M, García-Luis J, Marfil S, Olivares I, Estévez-Herrera J, Trujillo-González R, Blanco J, Lopez-Galindez C. Biomedicines. 2022 Sep 2,10(9):2172.
PUBMED DOIPrevalence of HIV-1 dual infection in LTNP-Elite Controllers
María Pernas, Concepción Casado, Virginia Sandonis, Carolina Arcones, Carmen Rodríguez , Ezequiel Ruiz-Mateos , Eva Ramírez de Arellano , Norma Rallón , Margarita Del Val , Eulalia Grau, Mariola López-Vazquez , Manuel Leal , Jorge del Romero , Cecilio López Galíndez . (2013). J.of AIDS. 64, 3, 225-231. IF 4.262
PUBMED DOIA Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Retroviral Control.
Istvan Bartha Jonathan M Carlson, Chanson J Brumme, Paul J McLaren, Zabrina L Brumme, Mina John, David W Haas, Javier Martinez-Picado, Cecilio López Galíndez, Andri Rauch, Huldrych F Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Jennifer Listgarten, Nico Pfeifer, Zoltan Kutalik, Todd M Allen, Viktor Müller, P Richard Harrigan, David Heckerman, Amalio Telenti, and Jacques Fellay, for the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study. (2013). Elife. 2013;2:e01123
PUBMED DOIFactors Leading to the Loss of Natural Elite Control of HIV-1 Infection
Pernas M, Tarancón-Diez L, Rodríguez-Gallego E, Gómez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, León A, Rodriguez C, Benito JM, Rallón N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, García F, Alcamí J, Muñoz-Fernández M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. J Virol. 2018 Feb 12,92(5): e01805-17
PUBMED DOIContent with Investigacion .
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Leticia Bernal Martínez
Staff Scientist
ORCID code: 0000-0002-1694-5522
Dr. Bernal-Martínez obtained her degree in Biochemistry from the University of Zaragoza in 2005. She joined the Mycology Reference and Research Laboratory (LRIM) in 2006 under a trainee contract and completed her PhD within the Official Doctoral Program in Microbiology and Parasitology at the Complutense University of Madrid, defending her thesis in 2010 with highest honors (Cum Laude). In 2007, she continued her research activity at LRIM within the framework of the Spanish Network for Research in Infectious Diseases (REIPI). In 2016, she completed a Postgraduate Diploma in Promotion and Management of International Projects (Technical University of Madrid) and undertook a research stay at the Microbiology and Infection Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho (Braga, Portugal). She was subsequently appointed as a PhD researcher within the Biomedical Research Networking Center in Infectious Diseases (CIBERINFEC). Since 2024, she serves as Specialist Scientist at the Carlos III Health Institute (ISCIII) and is responsible for the Diagnostic and Serology Section for Endemic Fungi at the Mycology Reference and Research Laboratory.
Dr. Bernal-Martínez has authored more than 30 peer-reviewed scientific publications and two book chapters. She has actively participated in over 12 research projects and has presented her work at numerous national and international scientific conferences. Her research has focused on human fungal infections, antifungal resistance, therapeutic drug monitoring, genetic variants associated with antifungal metabolism, and the identification of predictive biomarkers of invasive fungal infections. However, her primary expertise lies in the diagnostic field, particularly in the design, optimization, and validation of real-time PCR–based methodologies.
She is currently Principal Investigator of a research project aimed at improving current diagnostic techniques for invasive fungal infections, evaluating emerging diagnostic technologies, and studying primary fungal pathogens. A substantial part of her work has been transferred to the Spanish National Health System and to research centers in Latin America. Many of the diagnostic methodologies developed have been incorporated into the official service portfolio of ISCIII. She has collaborated with multiple hospitals through research projects and clinical trials applying these technologies, as well as with the ISCIII spin-off company Micomol S.L.
Dr. Bernal-Martínez has supervised several Master’s and Undergraduate Final Degree Projects from students at the Complutense University of Madrid and the University of Alcalá. She is a member of the teaching staff of the UNED-ISCIII PhD Program in Biomedical Sciences and Public Health and serves as lecturer in the Master’s Program in Public Health and Research in Infectious Diseases at the University of Alcalá. -
Laura Alcázar Fuoli
Research Scientist
Graduated in Biochemistry from the Autonomous University of Madrid and PhD in Biology from the Complutense University of Madrid in 2006. She completed her doctoral thesis at the National Center of Microbiology (CNM) under the direction of Dr. Emilia Mellado, in the study of the synthesis of Ergosterol in Aspergillus fumigatus. In 2012 Laura joined the reference laboratory in mycology with a researcher contract for the “Miguel Servet” program after having worked for three years as an associate researcher at Imperial College London. During that period his research focused on host adaptation mechanisms and virulence factors of A. fumigatus. In 2014 he obtained the position of Senior Scientist of Public Research Organizations carrying out his research work at the CNM.
List of staff
Additional Information
Contact Information
María Teresa Coiras
918223782
mcoiras@isciii.es
generic email: pirv.isciii@gmail.com
Scientific Societies
• Spanis Society for Infectious Diseases and Clinical Microbiology (SEIMC).
• AIDS Study Group (GeSIDA) of SEIMC.
• PIRV is member of the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC, group CB21/13/00015).
Other links
You can follow the activity of our group in Twitter (X), Instagram and Linkedin.
Collaboration in other projects
Project Title: Rectal microbiota as a factor associated with vulnerability to repeated sexually transmitted infections. Microsex Studio
Principal investigators: Vicente Estrada Pérez (San Carlos Clinical Hospital)
Financing agency: Strategic Action in Health (AES) 2023
Participating entities: San Carlos Clinical Hospital, ISCIII
Duration: 01/01/2024-12/31/2026. Contract/project file: PI23/01545
Project title: Prospective, observational, longitudinal, multicenter study to evaluate clinical efficacy, safety and immunogenicity developed in individuals with Philadelphia-negative Chronic Myeloproliferative Neoplasms treated with JAK inhibitors after receiving full vaccination with Adjuvanted Herpes Zoster Subunit vaccine (Shingrix)
Principal investigators: Valentín García Gutiérrez (Hospital Univ Ramón y Cajal)
Funding agency: GSK Glaxo Smithkline
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024 – 12/31/2024
Project title: Infection in Solid Organ Transplant recipients: correlation with immune function. Identification of predictive biomarkers and feasibility evaluation with CD45RAneg cell therapy
Principal investigators: Alejandro Luna de Abia, Jesús Fortún (Univ Ramón y Cajal Hospital)
Financing agency: Strategic Health Action (AES) 2023
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024-12/31/2026
Contract/project file: PI23/01924
Project title: Evaluation of the levels of the System associated with BLyS in patients with post-infectious syndromes and dysautonomic alterations of the heart rhythm
Principal researcher: Pablo Guisado
Funding agency: Spanish Society of Internal Medicine SEMI.
Participating entities: ISCIII, Quironsalud Research Institute for Research and Innovation
Duration 2023-2025
Project title: HIV Open Science (dissemination project)
Principal researcher: Eva Poveda
Financing agency: Spanish Foundation for Science and Technology (FECYT), Call for aid for the Promotion of Scientific, Technological and Innovation Culture.
Participating entities: ISCIII, Fundación Biomédica Galicia Sur, IrsiCaixa, Hospital Vall d’Hebron, Hospital de la Princesa, Fundación Imagina Más, Institute of Biomedicine of Seville (IBIS), Case Western Reserve University (Cleveland, Ohio)
Duration 2023-2024
Contract/project file: 17715
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV (Annual renewal).
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2023 – 04/01/2024
Contract/project file: 1,013,006
Project title: Clinical and microbiological impact of the monkeypox virus outbreak in patients in Spain (2022): multicenter project MONKPOX-ESP22, Work package 4, virological research.
Principal researcher: Anabel Negredo (WP4 coordinator); Maria Paz Sánchez Seco (general coordinator)
Financing agency: CIBERINFEC/CIBERESP ISCIII Strategic Action.
Participating entities: ISCIII
Duration July 2022 - May 2023
Contract/project file: MONKPOX-ESP22
Project title: Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition.
Principal investigator: Gemma Moncunill Piñas (IP); Marta Massanella (coIP); María Teresa Coiras López (co-PI)
Financing agency: CIBERINFEC Strategic Action.
Participating entities: ISCIII, IS-Global, IrsiCaixa
Duration 07/28/2022-07/29/2024
Contract/project file: IM22/INF/5
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV.
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2022 – 04/01/2023
Contract/project file: 1,013,006
Project title: Characterization of the immune response developed after vaccination with COVID-19 in patients with hematological malignancies.
Principal researcher: Valentín García Gutiérrez
Funding agency: Ministry of Science and Innovation, PI21 - Health research projects (AES 2021). Health research project modality.
Participating entities: ISCIII, Ramón y Cajal University Hospital
Duration 01/01/2022 – 12/31/2024
Contract/project file: PI21_00877
Contact Information
María Teresa Coiras
918223782
mcoiras@isciii.es
generic email: pirv.isciii@gmail.com
Scientific Societies
• Spanis Society for Infectious Diseases and Clinical Microbiology (SEIMC).
• AIDS Study Group (GeSIDA) of SEIMC.
• PIRV is member of the Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC, group CB21/13/00015).
Other links
You can follow the activity of our group in Twitter (X), Instagram and Linkedin.
Collaboration in other projects
Project Title: Rectal microbiota as a factor associated with vulnerability to repeated sexually transmitted infections. Microsex Studio
Principal investigators: Vicente Estrada Pérez (San Carlos Clinical Hospital)
Financing agency: Strategic Action in Health (AES) 2023
Participating entities: San Carlos Clinical Hospital, ISCIII
Duration: 01/01/2024-12/31/2026. Contract/project file: PI23/01545
Project title: Prospective, observational, longitudinal, multicenter study to evaluate clinical efficacy, safety and immunogenicity developed in individuals with Philadelphia-negative Chronic Myeloproliferative Neoplasms treated with JAK inhibitors after receiving full vaccination with Adjuvanted Herpes Zoster Subunit vaccine (Shingrix)
Principal investigators: Valentín García Gutiérrez (Hospital Univ Ramón y Cajal)
Funding agency: GSK Glaxo Smithkline
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024 – 12/31/2024
Project title: Infection in Solid Organ Transplant recipients: correlation with immune function. Identification of predictive biomarkers and feasibility evaluation with CD45RAneg cell therapy
Principal investigators: Alejandro Luna de Abia, Jesús Fortún (Univ Ramón y Cajal Hospital)
Financing agency: Strategic Health Action (AES) 2023
Participating entities: IRYCIS, ISCIII
Duration: 01/01/2024-12/31/2026
Contract/project file: PI23/01924
Project title: Evaluation of the levels of the System associated with BLyS in patients with post-infectious syndromes and dysautonomic alterations of the heart rhythm
Principal researcher: Pablo Guisado
Funding agency: Spanish Society of Internal Medicine SEMI.
Participating entities: ISCIII, Quironsalud Research Institute for Research and Innovation
Duration 2023-2025
Project title: HIV Open Science (dissemination project)
Principal researcher: Eva Poveda
Financing agency: Spanish Foundation for Science and Technology (FECYT), Call for aid for the Promotion of Scientific, Technological and Innovation Culture.
Participating entities: ISCIII, Fundación Biomédica Galicia Sur, IrsiCaixa, Hospital Vall d’Hebron, Hospital de la Princesa, Fundación Imagina Más, Institute of Biomedicine of Seville (IBIS), Case Western Reserve University (Cleveland, Ohio)
Duration 2023-2024
Contract/project file: 17715
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV (Annual renewal).
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2023 – 04/01/2024
Contract/project file: 1,013,006
Project title: Clinical and microbiological impact of the monkeypox virus outbreak in patients in Spain (2022): multicenter project MONKPOX-ESP22, Work package 4, virological research.
Principal researcher: Anabel Negredo (WP4 coordinator); Maria Paz Sánchez Seco (general coordinator)
Financing agency: CIBERINFEC/CIBERESP ISCIII Strategic Action.
Participating entities: ISCIII
Duration July 2022 - May 2023
Contract/project file: MONKPOX-ESP22
Project title: Biomarkers and underlying immunopathological mechanisms of post COVID-19 condition.
Principal investigator: Gemma Moncunill Piñas (IP); Marta Massanella (coIP); María Teresa Coiras López (co-PI)
Financing agency: CIBERINFEC Strategic Action.
Participating entities: ISCIII, IS-Global, IrsiCaixa
Duration 07/28/2022-07/29/2024
Contract/project file: IM22/INF/5
Project title: Identification of immunological biomarkers associated with the cellular and humoral immune response related to vaccination against SARS-CoV-2 in patients with HIV.
Principal investigator: Rafael Rodríguez Rosado
Funding agency: Alfonso X El Sabio University-Santander Universities. XIII Call for Research Projects.
Participating entities: ISCIII, Severo Ochoa University Hospital
Duration 04/01/2022 – 04/01/2023
Contract/project file: 1,013,006
Project title: Characterization of the immune response developed after vaccination with COVID-19 in patients with hematological malignancies.
Principal researcher: Valentín García Gutiérrez
Funding agency: Ministry of Science and Innovation, PI21 - Health research projects (AES 2021). Health research project modality.
Participating entities: ISCIII, Ramón y Cajal University Hospital
Duration 01/01/2022 – 12/31/2024
Contract/project file: PI21_00877