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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
Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene.
Matamala N, Aggarwal N, Iadarola P, Fumagalli M, Gomez-Mariano G, Lara B, Martinez MT, Cuesta I, Stolk J, Janciauskiene S, Martinez-Delgado B. Identification of Novel Short C-Terminal Transcripts of Human SERPINA1 Gene. PLoS One. 2017 Jan 20;12(1):e0170533.
PUBMED DOIA case of respiratory toxigenic diphtheria: Contact tracing results and considerations following a 30-year disease-free interval, Catalonia, Spain, 2015.
Jané, M., Vidal, M.J., Camps, N., Campins, M., Martínez, A., Balcells, J., Martin-Gomez, M.T., Bassets, G., Herrera-Leon, S., Foguet, A., Maresma, M., Follia, N., Uriona, S., Pumarola, T. A case of respiratory toxigenic diphtheria: Contact tracing results and considerations following a 30-year disease-free interval, Catalonia, Spain, 2015. (2018) Eurosurveillance, 23 (13).
PUBMED DOIDevelopment of three multiplex PCR assays targeting the 21 most clinically relevant serogroups associated with Shiga toxin-producing E. coli infection in humans
Sánchez, S., Llorente, M.T., Echeita, M.A., Herrera-León, S. Development of three multiplex PCR assays targeting the 21 most clinically relevant serogroups associated with Shiga toxin-producing E. coli infection in humans (2015) PLoS ONE, 10 (1).
PUBMED DOIShiga toxin-producing Escherichia coli and atypical enteropathogenic E. coli infection in a Spanish household
Sánchez, S., Cenoz, M.G., Martín, C., Beristain, X., Llorente, M.T., Herrera-León, S. Cluster investigation of mixed O76:H19 Shiga toxin-producing Escherichia coli and atypical enteropathogenic E. coli infection in a Spanish household (2014) Epidemiology and Infection, 142 (5), pp. 1029-1033.
PUBMED DOIOff-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.
Palladino C, Navarro Gomez ML, Soler-Palacin P, Gonzalez-Tome MI, Jiménez de Ory S, Espiau M, Pérez-Hoyos S, León-Leal JA, Méndez M, Moreno-Pérez D, Fortuny C, uer A, Pocheville I, Moreno S, Briz V, on behalf of the CoRISpe Working Group. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice. AIDS 2015; 29-16, pp.2155-2159. (A; FI= 4,407; Q1 Infectious Disease).
PUBMED DOIComparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.
Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. Avellon A, Morago L, Garcia-Galera del Carmen M, Munoz M, Echevarría JM. J Med Virol. 2015 Nov;87(11):1934-9. Epub 2015 May 29.
PUBMED DOIRelative telomere length impact on mortality of COVID-19: sex differences.
Virseda-Berdices A, Concostrina-Martinez L, Martínez-González O, Blancas R, Resino S, Ryan P, De Juan C, Moreira-Escriche P, Martin-Vicente M, Brochado-Kith O, Blanca-López N, Jiménez-Sousa MA (‡,*), Fernández-Rodríguez A (‡). Relative telomere length impact on mortality of COVID-19: sex differences. J Med Virol 2023; 98 (1): e28368 (A; FI= 20.96; D1, Virology; JCR 2021).
PUBMEDActivity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide
García-Quintanilla, M., Pulido, M. R., Moreno-Martínez, P., Martín-Peña, R., López-Rojas, R., Pachón, J. and McConnell, M.J.* Activity of host antimicrobials against multidrug resistant Acinetobacter baumannii acquiring colistin resistance through loss of lipopolysaccharide. Antimicrobial Agents and Chemotherapy 2014. May;58(5):2972-5.
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
Doctoral theses
“Expression and functionality of tlr2 and tlr4 in lymphomyeloid populations present in the lung and lymphoid organs during embryonic and neonatal life in mouse models.” Carolina Ruiz Sánchez. Complutense University of Madrid, 2022
Master's thesis
Detection and characterization of extracellular vesicles of platelet origin in lung supernatants from SPN-infected animals. Marta Paris, Alcalá University, 2024
Study of TLR-dependent activation in the RAW 264.7 macrophage line. Iñigo Merino de Saracho, Alcalá University, 2023
Study of the functionality of TLR receptors in the lung and other lymphoid organs in B cell populations using the neonatal mouse model. Yolanda Campanero, Alcalá University, 2023
Exploratory study of T lymphoid progenitors in the neonatal mouse lung. Alejandro Arrabal, Complutense University of Madrid, 2022
Study of B lymphoid differentiation in mice deficient for CD5 and CD6 molecules. Cristina Martín, Alcalá University, 2022
Role of platelets and their progenitor cells in two animal models of infection: SPN and RSV. Ana de Lucas Rius, Alcalá University, 2020
Pilot study of RSV infection in the mouse model: cellular phenotype of myeloid and lymphoid populations in the lung in two animal models of infection: SPN and RSV. Juan Antonio Martín Quesada, Alcalá University, 2020
B cell response during Streptococcus pneumoniae infection. Eva Castro, 2020
Study of the hematopoietic potential of neonatal lung cells in the mouse model. Ana Cogollo García, Alcalá University, 2018
Innate immune response to S. pneumoniae in the lung. Rodrigo Sánchez, Complutense University of Madrid, 2018
Neonatal immunity in the mouse model: localization and function of the innate and adaptive response. Alba Ezequiel Fernández, Alcalá University, 2017
Characterization of immunoglobulin gene diversity in the mouse model of TLR4 homeostasis and activation by bacterial lipopolysaccharide. Cristina García Caballero, Alcalá University, 2017
Altered lymphopoiesis and splenic B cell subsets on Telomerase Activity Deficient Mice (TERC-/-). Juliana Manosalva, Complutense University of Madrid, 2017
Study of the Immune Response in Nasopharyngeal Washings of Infants with Bronchiolitis. Isabel Martín Barrios, Complutense University of Madrid, 2016
Dynamics of B1-REL lymphocytes in the in vivo immunization model with DNP-LPS. Inmaculada Sanz Ramos University Alcalá, 2015
Megakaryocyte differentiation pathways in the mouse model. Marta Cobos Briz, Alcalá University, 2015
Role of megakaryocytes in infectious processes. Melania Guerrero Hue, Complutense University of Madrid, 2015
Final degree projects
Study of new bacterial vaccines in the mouse (Mus musculus) infection model due to Streptococcus pneumoniae. Alejandro Arrabal, Polytechnic University of Madrid, 2021
Megakaryocytes and platelets in SPN respiratory infection: Role of TLR4. Óscar González Hervás, Complutense University of Madrid, 2021
Study of the immune response mediated by pseudo-innate B lymphocytes against TLR4-dependent immunization models. Rodrigo Sánchez, Complutense University of Madrid, 2017.
Study of the diversity in the immunoglobulin repertoire in healthy individuals. Isabel Martín, Francisco de Vitoria University, 2015.
Dynamics of hematopoietic populations in the perinatal spleen. Inmaculada Sanz, Alcalá University, 2014
Teaching in training courses
Training course: Introduction to Flow Cytometry (from 2015 to present)
Training Course: Flow Cytometry Data Analysis (2018 to present)
Outreach / Citizen Science
• Collaboration in the 4th+Company CAM program.
• Collaboration with the ISCIII Scientific Culture Unit in Science Week at the ISCIII
• Scientific Dissemination Project "Talking about Science", carried out in Majadahonda primary, secondary and high school schools, since 2015 in collaboration with the Department of Education and Youth of the Majadahonda City Council: “How your Immune System works and healthy lifestyle habits to take care of it”
Doctoral theses
“Expression and functionality of tlr2 and tlr4 in lymphomyeloid populations present in the lung and lymphoid organs during embryonic and neonatal life in mouse models.” Carolina Ruiz Sánchez. Complutense University of Madrid, 2022
Master's thesis
Detection and characterization of extracellular vesicles of platelet origin in lung supernatants from SPN-infected animals. Marta Paris, Alcalá University, 2024
Study of TLR-dependent activation in the RAW 264.7 macrophage line. Iñigo Merino de Saracho, Alcalá University, 2023
Study of the functionality of TLR receptors in the lung and other lymphoid organs in B cell populations using the neonatal mouse model. Yolanda Campanero, Alcalá University, 2023
Exploratory study of T lymphoid progenitors in the neonatal mouse lung. Alejandro Arrabal, Complutense University of Madrid, 2022
Study of B lymphoid differentiation in mice deficient for CD5 and CD6 molecules. Cristina Martín, Alcalá University, 2022
Role of platelets and their progenitor cells in two animal models of infection: SPN and RSV. Ana de Lucas Rius, Alcalá University, 2020
Pilot study of RSV infection in the mouse model: cellular phenotype of myeloid and lymphoid populations in the lung in two animal models of infection: SPN and RSV. Juan Antonio Martín Quesada, Alcalá University, 2020
B cell response during Streptococcus pneumoniae infection. Eva Castro, 2020
Study of the hematopoietic potential of neonatal lung cells in the mouse model. Ana Cogollo García, Alcalá University, 2018
Innate immune response to S. pneumoniae in the lung. Rodrigo Sánchez, Complutense University of Madrid, 2018
Neonatal immunity in the mouse model: localization and function of the innate and adaptive response. Alba Ezequiel Fernández, Alcalá University, 2017
Characterization of immunoglobulin gene diversity in the mouse model of TLR4 homeostasis and activation by bacterial lipopolysaccharide. Cristina García Caballero, Alcalá University, 2017
Altered lymphopoiesis and splenic B cell subsets on Telomerase Activity Deficient Mice (TERC-/-). Juliana Manosalva, Complutense University of Madrid, 2017
Study of the Immune Response in Nasopharyngeal Washings of Infants with Bronchiolitis. Isabel Martín Barrios, Complutense University of Madrid, 2016
Dynamics of B1-REL lymphocytes in the in vivo immunization model with DNP-LPS. Inmaculada Sanz Ramos University Alcalá, 2015
Megakaryocyte differentiation pathways in the mouse model. Marta Cobos Briz, Alcalá University, 2015
Role of megakaryocytes in infectious processes. Melania Guerrero Hue, Complutense University of Madrid, 2015
Final degree projects
Study of new bacterial vaccines in the mouse (Mus musculus) infection model due to Streptococcus pneumoniae. Alejandro Arrabal, Polytechnic University of Madrid, 2021
Megakaryocytes and platelets in SPN respiratory infection: Role of TLR4. Óscar González Hervás, Complutense University of Madrid, 2021
Study of the immune response mediated by pseudo-innate B lymphocytes against TLR4-dependent immunization models. Rodrigo Sánchez, Complutense University of Madrid, 2017.
Study of the diversity in the immunoglobulin repertoire in healthy individuals. Isabel Martín, Francisco de Vitoria University, 2015.
Dynamics of hematopoietic populations in the perinatal spleen. Inmaculada Sanz, Alcalá University, 2014
Teaching in training courses
Training course: Introduction to Flow Cytometry (from 2015 to present)
Training Course: Flow Cytometry Data Analysis (2018 to present)
Outreach / Citizen Science
• Collaboration in the 4th+Company CAM program.
• Collaboration with the ISCIII Scientific Culture Unit in Science Week at the ISCIII
• Scientific Dissemination Project "Talking about Science", carried out in Majadahonda primary, secondary and high school schools, since 2015 in collaboration with the Department of Education and Youth of the Majadahonda City Council: “How your Immune System works and healthy lifestyle habits to take care of it”