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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
Frecuencia de sustituciones relevantes asociadas a resistencia en la región NS5A a elbasvir en el virus de la hepatitis C en pacientes con genotipo 1a en España
2. Palladino C, Esteban-Cartelle B, Mate-Cano I, Sánchez-Carrillo M, Resino S, Briz V. Frecuencia de sustituciones relevantes asociadas a resistencia en la región NS5A a elbasvir en el virus de la hepatitis C en pacientes con genotipo 1a en España Enferm Infecc Microbiol Clin. 2018; 36 (5): 262-267. (A; FI= 1.707; Q2 Microbiology).
PUBMED DOIDevelopment of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides.
4. Briz V, Sepulveda-Crespo D, Diniz AR; Borrego P, Rodes B; Javier de la Mata F, Gomez R, Taveira N, Muñoz-Fernandez MA. Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides. Nanoscale 2015, 7(35): 14669-14683. (A; FI= 7.76; D1 Materials Science, Multidisciplinary).
PUBMED DOIHepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.
6. Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017. Ndumbi P, Freidl GS, Williams CJ, Mårdh O, Varela C, Avellón A, …. Severi E; Members Of The European Hepatitis A Outbreak Investigation Team. Euro Surveill. 2018 Aug;23(33). doi: 10.2807/1560-7917.ES.2018.23.33.1700641.
PUBMED DOIDetection of hepatitis C virus (HCV) core-specific antibody suggests occult HCV infection among blood donors
7. Detection of hepatitis C virus (HCV) core-specific antibody suggests occult HCV infection among blood donors. Quiroga JA, Avellón A, Bartolomé J, Andréu M, Flores E, González MI, González R, Pérez S, Richart LA, Castillo I, Alcover J, Palacios R, Carreño V, Echevarría JM. Transfusion. 2016 Jul;56(7):1883-90. Epub 2016 May 17.
PUBMED DOIHepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15.
8. Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15. Adlhoch C, Avellon A, Baylis SA, Ciccaglione AR, Couturier E, de Sousa R, Epštein J, Ethelberg S, Faber M, Fehér Á, Ijaz S, Lange H, Manďáková Z, Mellou K, Mozalevskis A, Rimhanen-Finne R, Rizzi V, Said B, Sundqvist L, Thornton L, Tosti ME, van Pelt W, Aspinall E, Domanovic D, Severi E, Takkinen J, Dalton HR. J Clin Virol. 2016 Sep;82:9-16. Epub 2016 Jun 23.
PUBMED DOIFull coding hepatitis E virus genotype 3 genome amplification method
9. Full coding hepatitis E virus genotype 3 genome amplification method. Muñoz-Chimeno M, Forero JE, Echevarría JM, Muñoz-Bellido JL, Vázquez-López L, Morago L, García-Galera MC, Avellón A. J Virol Methods. 2016 Apr;230:18-23. Epub 2016 Jan 16.
PUBMED DOIAntigenicity of Leishmania-Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters
2. Fernández L, Carrillo E, Sánchez-Sampedro L, Sánchez C, Ibarra-Meneses AV, Jimenez MA, Almeida VDA, Esteban M, Moreno J. Antigenicity of Leishmania-Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters. Front Immunol. 2018 Apr 23;9:843.
PUBMED DOIInterleukin-2 as a marker for detecting asymptomatic individuals in areas where Leishmania infantum is endemic.
5. Ibarra-Meneses AV, Carrillo E, Sánchez C, García-Martínez J, López Lacomba D, San Martin JV, Alves F, Alvar J, Moreno J. Interleukin-2 as a marker for detecting asymptomatic individuals in areas where Leishmania infantum is endemic. Clin Microbiol Infect. 2016 Aug;22(8):739.e1-4.
PUBMED DOIProtein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis.
7. Carrillo E, Jimenez MA, Sanchez C, Cunha J, Martins CM, da Paixão Sevá A, Moreno J. Protein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis. PLoS One. 2014 Feb 25;9(2):e89412.
PUBMED DOIMolecular typing of Leishmania infantum isolates from a leishmaniasis outbreak in Madrid, Spain, 2009 to 2012
9. Chicharro C, Llanes-Acevedo IP, García E, Nieto J, Moreno J, Cruz I. Molecular typing of Leishmania infantum isolates from a leishmaniasis outbreak in Madrid, Spain, 2009 to 2012. Euro Surveill. 2013 Jul 25;18(30):20545.
PUBMED DOIHigh levels of anti-Phlebotomus perniciosus saliva antibodies in different reservoirs from the re-emerging leishmaniasis focus in Madrid, Spain.
2. Martín-Martín I, Molina R, Rohoušová I, Drahota J., Volf P, Jiménez M. High levels of anti-Phlebotomus perniciosus saliva antibodies in different reservoirs from the re-emerging leishmaniasis focus in Madrid, Spain. Vet Parasitol 2014, 202: 207–216.
PUBMED DOICould wild rabbits (Oryctolagus cuniculus) be reservoirs for Leishmania infantum in the focus of Madrid, Spain?
3. Jiménez M, González E, Martín-Martín I, Hernández S, Molina R. Could wild rabbits (Oryctolagus cuniculus) be reservoirs for Leishmania infantum in the focus of Madrid, Spain?. Vet Parasitol 2014, 202: 296–300.
PUBMED DOIReview of ten-years presence of Aedes albopictus in Spain 2004–2014: known distribution and public health concerns.
5. Collantes F, Delacour S, Alarcón-Elbal PM, Ruiz-Arrondo I, Delgado JA, Torrell-Sorio A, Bengoa M, Eritja R, Miranda MA, Molina R, Lucientes J. Review of ten-years presence of Aedes albopictus in Spain 2004–2014: known distribution and public health concerns. Parasit Vectors. 2015 Dec 23;8:655.
PUBMED DOIPhleboviruses detection in Phlebotomus perniciosus from a human leishmaniasis focus in South-West Madrid region, Spain.
6. Remoli ME, Jiménez M, Fortuna C, Benedetti E, Marchi A, Genovese D, Gramiccia M, Molina R, Ciufolini MG. Phleboviruses detection in Phlebotomus perniciosus from a human leishmaniasis focus in South-West Madrid region, Spain. Parasit Vectors 2016, 9:205.
PUBMED DOIInfectivity of Post-Kala-azar Dermal Leishmaniasis patients to sand flies: revisiting a proof of concept in the context of the Kala-azar Elimination Program in the Indian subcontinent.
7. Molina R, Ghosh D, Carrillo E, Monnerat S, Bern C, Mondal D, Alvar J. Infectivity of Post-Kala-azar Dermal Leishmaniasis patients to sand flies: revisiting a proof of concept in the context of the Kala-azar Elimination Program in the Indian subcontinent. Clin Infect Dis 2017, 65:
PUBMED DOIPrevalence and molecular characterization of Strongyloides stercoralis, Giardia duodenalis, Cryptosporidium spp., and Blastocystis spp. isolates in schoolchildren in Cubal, Central Angola
2. Dacal E, Saugar JM, de Lucio A, Hernández de Mingo M, Robinson E, Aznar Ruiz de Alegría ML, Espasa M, Ninda A, Gandasegui J, Sulleiro E, Moreno M, Salvador F, Molina I, Rodríguez E, Carmena D. 2018. Prevalence and molecular characterization of Strongyloides stercoralis, Giardia duodenalis, Cryptosporidium spp., and Blastocystis spp. isolates in schoolchildren in Cubal, Central Angola. Parasites and Vectors, 11: 67.
PUBMED DOIMolecular diversity and frequency of the diarrheagenic enteric protozoan Giardia duodenalis and Cryptosporidium spp. in a hospital setting in Northern Spain.
3. Azcona-Gutiérrez JM, de Lucio A, Hernández-de-Mingo M, García-García C, Soria-Blanco LM, Morales L, Aguilera M, Fuentes I, Carmena D. 2017. Molecular diversity and frequency of the diarrheagenic enteric protozoan Giardia duodenalis and Cryptosporidium spp. in a hospital setting in Northern Spain. PLoS One, 12: e0178575.
PUBMED DOIDetection of zoonotic protozoa Toxoplasma gondii and Sarcocystis suihominis in wild boars from Spain. Zoonoses Public Health
4. Calero-Bernal, R., Pérez-Martín, J.E., Reina, D., Serrano, F.J., Frontera, E., Fuentes, I, Dubey, J.P., 2016. Detection of zoonotic protozoa Toxoplasma gondii and Sarcocystis suihominis in wild boars from Spain. Zoonoses Public Health. 63:346-50
PUBMED DOIEpidemiological and clinical profile of adult patients with Blastocystis sp. infection in Barcelona, Spain.
5. Salvador F, Sulleiro E, Sánchez-Montalvá A, Alonso C, Santos J, Fuentes I, Molina I. 2016; Epidemiological and clinical profile of adult patients with Blastocystis sp. infection in Barcelona, Spain. Parasit Vectors; 9:548.
PUBMED DOIPrevalence and genetic diversity of Giardia duodenalis and Cryptosporidium spp. among schoolchildren in a rural area of the Amhara Region, North-West Ethiopia
6. de Lucio A, Amor-Aramendía A, Bailo B, Saugar JM, Anegagrie M, Arroyo A, López-Quintana B, Zewdie D, Ayehubizu Z, Yizengaw E, Abera B, Yimer M, Mulu W, Hailu T, Herrador Z, Fuentes I, Carmena D. 2016. Prevalence and genetic diversity of Giardia duodenalis and Cryptosporidium spp. among schoolchildren in a rural area of the Amhara Region, North-West Ethiopia. PLoS One 11: e0159992.
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