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Content with Investigacion Susceptibilidad del huésped a las infecciones fúngicas invasoras .

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

Research projects

Content with Investigacion Susceptibilidad del huésped a las infecciones fúngicas invasoras .

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Senescent accelerated prone 8 (SAMP8) mice as a model of age dependent neuroinflammation

Fernández A, Quintana E, Velasco P, Moreno-Jimenez B, de Andrés B, Gaspar ML, Liste I, Vilar M, Mira E, Cano E. J Neuroinflammation 2021 Mar 18;18(1):75.

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Interregional spread in Spain of linezolid-resistant Enterococcus spp. isolates carrying the optrA and poxtA genes.

7. Interregional spread in Spain of linezolid-resistant Enterococcus spp. isolates carrying the optrA and poxtA genes. Autores: Moure Z, Lara N, Marín M, Sola-Campoy PJ, Bautista V, Gómez-Bertomeu F, Gómez-Dominguez C, Pérez-Vázquez M, Aracil B, Campos J, Cercenado E, Oteo-Iglesias J; Spanish Linezolid-Resistant Enterococci Collaborating Group. Revista: Int J Antimicrob Agents. 2020 Jun;55(6):105977.

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Systematic analysis of intracellular trafficking motifs located within the cytoplasmic domain of simian immunodeficiency virus glycoprotein gp41

Postler TS, Bixby JG, Desrosiers RC, Yuste E; PLoS One. 2014 Dec 5;9(12):e114753

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Aspergillus fumigatus can exhibit persistence to the fungicidal drug voriconazole

Valero C., Á Mato-López, I J. Donaldson, A. Roldán, H. Chown, N. Van-Rhijn, S. Gago, T. Furukawa, A. Mogorovsky, R. Ben Ami, P. Bowyer, N. Osherov, T. Fontaine, G.H. Goldman, E. Mellado, M. Bromley and J. Amich. Microbiology Spectrum.2023 13;11(2):e0477022

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Antimicrobial-resistant Neisseria gonorrhoeae in Europe in 2020 compared with in 2013 and 2018: a retrospective genomic surveillance study.

Golparian D, Cole MJ, Sánchez-Busó L, Day M, Jacobsson S, Uthayakumaran T, Abad R, Bercot B, Caugant DA, Heuer D, Jansen K, Pleininger S, Stefanelli P, Aanensen DM, Bluemel B, Unemo M; Euro-GASP study group. Lancet Microbe. 2024 May;5(5):e478-e488.

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Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)

8. Acosta Y.Y., Zafra M.P., Ojeda G., Bernardone I.S., Dianzani U., Portolés P., Rojo J.M. Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278). Cell. Mol. Life Sci. 2011 Sep;68(18):3065-79.

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Dynamics of a Sporadic Nosocomial Acinetobacter calcoaceticus-Acinetobacter baumannii Complex Population

Villalón P, Ortega M, Sáez-Nieto JA, Carrasco G, Medina-Pascual MJ, Garrido N, Valdezate S. (2019). Dynamics of a Sporadic Nosocomial Acinetobacter calcoaceticus-Acinetobacter baumannii Complex Population. 2019. Front Microbiol. 22;10:593

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Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins.

Martínez-Sernández V, Perteguer MJ, Mezo M, González-Warleta M, Gárate T, Valero MA, Ubeira FM. Fasciola spp: Mapping of the MF6 epitope and antigenic analysis of the MF6p/HDM family of heme-binding proteins. PLoS One. 2017 Nov 21;12(11):e0188520.

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HU of Streptococcus pneumoniae is essential for the preservation of DNA supercoiling

Ferrándiz MJ, Carreño D, Ayora S, de la Campa AG. Front Microbiol. 9:493 (2018).

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The TLR4-MyD88 Signaling Regulates Lung Monocyte Differentiation Pathways in Response to Streptococcus pneumoniae

Sánchez-Tarjuelo R, Cortegano I, Manosalva J, Rodríguez M, Ruiz C, Alía M, Prado MC, Cano EM, Ferrándiz MJ, de la Campa A, Gaspar ML, de Andrés B. Front Immunol 2020 Sep 16:11:2120.

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Carbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high-risk clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2.

8. Carbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high-risk clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2. Autores: Pérez-Vázquez M, Sola-Campoy PJ, Zurita ÁM, Ávila A, Gómez-Bertomeu F, Solís S, López-Urrutia L, Gónzalez-Barberá EM, Cercenado E, Bautista V, Lara N, Aracil B, Oliver A, Campos J, Oteo-Iglesias J; Spanish Antibiotic Resistance Surveillance Program collaborating Group. Revista: Int J Antimicrob Agents. 2020 Jul;56(1):106026.

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Evolution of broadly cross-reactive HIV-1-neutralizing activity: therapy-associated decline, positive association with detectable viremia, and partial restoration of B-cell subpopulations

Ferreira CB, Merino-Mansilla A, Llano A, Perez I, Crespo I, Llinas L, Garcia F, Gatell JM, Yuste E, Sanchez-Merino V; J Virol. 2013 Nov;87(22):12227-36

PUBMED DOI

COVID-19 Associated Pulmonary Aspergillosis (CAPA): Hospital or Home Environment as a source of life-threatening Aspergillus fumigatus infection?

Peláez-García de la Rasilla T, González-Jiménez I, García-Fernández Arroyo A, Roldán A, Carretero-Ares JL, Clemente-García M,, Martínez-Suarez M, Vázquez Valdés F, Melón-Garcia S, Mellado E, Sánchez-Nuñez ML on behalf HUCAPA group. Journal of Fungi, 2022 Mar 19;8(3):316.

PUBMED DOI

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV

Berzosa A, Guillen S, Epalza C, Escosa L, Navarro ML, Prieto LM, Sainz T, de Ory SJ, Montes M, Abad R, Vázquez JA, García IS, Ramos-Amador JT. Microorganisms. 2023 Dec 23;12(1):30

PUBMED DOI

Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain.

Valdezate S, Garrido N, Carrasco G, Medina-Pascual MJ, Villalón P, Navarro AM, Saéz-Nieto JA. Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain. J Antimicrob Chemother. 2017;72(3):754-761.

PUBMED DOI

Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions.

Morante T, Shepherd C, Constantinoiu C, Loukas A, Sotillo J. Revisiting the Ancylostoma caninum secretome provides new information on hookworm-host interactions. Proteomics. 2017 Dec;17(23-24).

PUBMED DOI

Boldine-derived alkaloids inhibit the activity of DNA topoisomerase I and growth of Mycobacterium tuberculosis.

García MT, Carreño D, Tirado-Vélez JM, Ferrándiz MJ, Rodrigues L, Gracia B, Amblar M, Ainsa JA*, de la Campa AG. Front Microbiol. 9:493 (2018).

PUBMED DOI

Nrf2 plays a protective role against intravascular hemolysis-mediated acute kidney injury.

Rubio-Navarro A, Vázquez-Carballo C, Guerrero-Hue M, García-Caballero C, Herencia C, Gutierrez E, Yuste C, Sevillano A, Praga M, Egea J, Cannata P, Cortegano I, de Andrés B, Gaspar ML, Cadenas S, Michalska P, León R, Ortiz, A, Egido J, Moreno JA. Front Pharmacol. 2019; 10: 740.

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Multidrug-resistant gram-negative bacteria in Spanish ICU patients: clinical and microbiological characterization (MURAN-UCI Project).

9. Multidrug-resistant gram-negative bacteria in Spanish ICU patients: clinical and microbiological characterization (MURAN-UCI Project). Autores: Ramirez de Arellano E, López-Causapé C, Delgado-Valverde M, Arroyo Muñoz FJ, Alemparte-Pardavila E, Arca-Suárez J, Ayestarán I, Calvo Montes J, Cañada-Garcia J, Garcia-Cobos S, García-Fernández S, Gijón Cordero D, González-López JJ, Mir-Cros A, Nuvials X, Pérez-Vázquez M, Pomares-de la Peña A, Pampín-Garcia M, Riazzo C, Rodríguez-Gómez J, Rojo-Molinero E, Ruiz-Garbajosa P, Soriano C, Suberviola Cañas B, Taltavull B, Garnacho-Montero J, Oliver Palomo A, Oteo-Iglesias J; MURAN-UCI Spanish group. Revista: Microbiol Spectr. 2026 Feb 3;14(2):e0298725.

PUBMED DOI

Human immunodeficiency virus type 1 and related primate lentiviruses engage clathrin through Gag-Pol or Gag

Popov S, Strack B, Sanchez-Merino V, Popova E, Rosin H, Gottlinger HG; J Virol. 2011 Apr;85(8):3792-801

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Content with Investigacion Susceptibilidad del huésped a las infecciones fúngicas invasoras .

List of staff

Additional Information

The Medical Entomology Laboratory has accumulated extensive experience in this field, especially in entomological field studies, biology of arthropods of medical interest, vector competence and vector control. Also, in the molecular detection of Leishmania infantum promastigotes in naturally parasitized phlebotomine sand flies, in the molecular identification of blood ingested by hematophagous arthropods and in the study of the immunomodulatory properties of proteins present in the saliva of phlebotomine sand flies and mosquitoes. Our laboratory is currently co-leading the studies of vectors and wild reservoirs of leishmaniasis in the leishmaniasis focus of Fuenlabrada, Madrid. In this sense, we have studied the role of asymptomatic individuals as reservoirs in the outbreak by xenodiagnosis. On the other hand, we have participated since 2007 in the Entomological Surveillance Program in Airports and Ports against Potential Vectors of Exotic Infectious Diseases, a program that is allowing to develop the expansion map in Spain of Aedes albopictus. In 2016-2017, we carried out surveillance of Ae. albopictus in the Community of Castilla-La Mancha. On the other hand, we conducted studies on the role of patients with post-kala-azar dermal leishmaniasis (PKDL) in the transmission of the parasite in Bangladesh and Sudan. In addition, we participate in research studying ticks transmitting Crimean-Congo hemorrhagic fever in Spain.

Currently, it maintains confidentiality agreements with several companies participating in the evaluation of molecules with activity against pathogens in vectors (GSK), in the development of vector traps using artificial intelligence algorithms (Irideon, Spain), and in the evaluation of repellents against phlebotomine sand flies (IRSEA, France).

The laboratory actively participates in outreach activities such as the Science Week or the European Researchers' Night, among others, making medical entomology science available to the general population.

The Medical Entomology Laboratory has accumulated extensive experience in this field, especially in entomological field studies, biology of arthropods of medical interest, vector competence and vector control. Also, in the molecular detection of Leishmania infantum promastigotes in naturally parasitized phlebotomine sand flies, in the molecular identification of blood ingested by hematophagous arthropods and in the study of the immunomodulatory properties of proteins present in the saliva of phlebotomine sand flies and mosquitoes. Our laboratory is currently co-leading the studies of vectors and wild reservoirs of leishmaniasis in the leishmaniasis focus of Fuenlabrada, Madrid. In this sense, we have studied the role of asymptomatic individuals as reservoirs in the outbreak by xenodiagnosis. On the other hand, we have participated since 2007 in the Entomological Surveillance Program in Airports and Ports against Potential Vectors of Exotic Infectious Diseases, a program that is allowing to develop the expansion map in Spain of Aedes albopictus. In 2016-2017, we carried out surveillance of Ae. albopictus in the Community of Castilla-La Mancha. On the other hand, we conducted studies on the role of patients with post-kala-azar dermal leishmaniasis (PKDL) in the transmission of the parasite in Bangladesh and Sudan. In addition, we participate in research studying ticks transmitting Crimean-Congo hemorrhagic fever in Spain.

Currently, it maintains confidentiality agreements with several companies participating in the evaluation of molecules with activity against pathogens in vectors (GSK), in the development of vector traps using artificial intelligence algorithms (Irideon, Spain), and in the evaluation of repellents against phlebotomine sand flies (IRSEA, France).

The laboratory actively participates in outreach activities such as the Science Week or the European Researchers' Night, among others, making medical entomology science available to the general population.

Content with Investigacion Biología y Variabilidad del VIH .