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Investigación
Special Pathogens
Líneas de investigación
Content with Investigacion .
Hepatitis
- Diseño de métodos diagnósticos para el estudio de los virus de las hepatitis (VH) A, B, C, D, E: Diseñamos sistemas de PCR para su detección y caracterización.
- Evaluación de métodos diagnósticos de los VH. Colaboramos con empresas para estudios de sensibilidad y especificidad de equipos diagnósticos.
- Estudios de Seroprevalencia de los virus de las hepatitis.
- Epidemiología genómica de genomas completos de VHA, VHB, VHC, VHD y VHE en colaboración con el ECDC. Estudios de trazabilidad del VHE.
- Caracterización molecular de virus de las hepatitis mediante secuenciación masiva: a) VHB: mutantes de escape HBsAg (prevalencia y efectos en la detección del HBsAg). Estudio de mutaciones en epítopos de estimulación inmune y mutaciones asociadas a evolución clínica desfavorable.
- b) VHC: resistencias a los antivirales de acción directa. Análisis molecular de subtipos poco frecuentes.
c) Estudios filogenéticos del VHD.
d) Análisis genómico del VHE.
e) Investigación etiológica de hepatitis no filiadas mediante estudios de metagenómica.
- b) VHC: resistencias a los antivirales de acción directa. Análisis molecular de subtipos poco frecuentes.
Publicaciones destacadas
9: Harvala H, Broberg E, Benschop K, Berginc N, Ladhani S, Susi P, Christiansen C, McKenna J, Allen D, Makiello P, McAllister G, Ca
9: Harvala H, Broberg E, Benschop K, Berginc N, Ladhani S, Susi P, Christiansen C, McKenna J, Allen D, Makiello P, McAllister G, Carmen M, Zakikhany K, Dyrdak R, Nielsen X, Madsen T, Paul J, Moore C, von Eije K, Piralla A, Carlier M, Vanoverschelde L, Poelman R, Anton A, López-Labrador FX, Pellegrinelli L, Keeren K, Maier M, Cassidy H, Derdas S, Savolainen-Kopra C, Diedrich S, Nordbø S, Buesa J, Bailly JL, Baldanti F, MacAdam A, Mirand A, Dudman S, Schuffenecker I, Kadambari S, Neyts J, Griffiths MJ, Richter J, Margaretto C, Govind S, Morley U, Adams O, Krokstad S, Dean J, Pons-Salort M, Prochazka B, Cabrerizo M, Majumdar M, Nebbia G, Wiewel M, Cottrell S, Coyle P, Martin J, Moore C, Midgley S, Horby P, Wolthers K, Simmonds P, Niesters H, Fischer TK. Recommendations for enterovirus diagnostics and characterisation within and beyond Europe. J Clin Virol. 2018 Apr; 101:11-17. doi: 10.1016/j.jcv.2018.01.008. Epub 2018 Feb 6. PMID: 29414181.
Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii
Inhibition of LpxC Increases Antibiotic Susceptibility in Acinetobacter baumannii. García-Quintanilla M, Caro-Vega JM, Pulido MR, Moreno-Martínez P, Pachón J, McConnell MJ. Antimicrob Agents Chemother. 2016 Jul 22;60(8):5076-9. doi: 10.1128/AAC.00407-16.
PUBMEDNew Panfungal Real-Time PCR Assay for Diagnosis of Invasive Fungal Infections.
4. Valero C, de la Cruz-Villar L, Zaragoza O, Buitrago MJ. New Panfungal Real-Time PCR Assay for Diagnosis of Invasive Fungal Infections. J Clin Microbiol. 2016 Dec;54(12):2910-2918. doi: 10.1128/JCM.01580-16. Epub 2016 Sep 14. PMID: 27629898.
DOIA Multiplex Real-Time PCR Assay for Identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in Samples from AIDS Patients with Opportunistic Pneumonia
6. Gago S, Esteban C, Valero C, Zaragoza O, Puig de la Bellacasa J, Buitrago MJ. A multiplex real-time PCR assay for identification of Pneumocystis jirovecii, Histoplasma capsulatum, and Cryptococcus neoformans/Cryptococcus gattii in samples from AIDS patients with opportunistic pneumonia. J Clin Microbiol. 2014 Apr;52(4):1168-76. doi: 10.1128/JCM.02895-13. Epub 2014 Jan 29. PMID: 24478409.
PUBMED DOIAnalysis of strain relatedness using High Resolution Melting in a case of recurrent candiduria
7. Gago S, Lorenzo B, Gomez-Lopez A, Cuesta I, Cuenca-Estrella M, Buitrago MJ. Analysis of strain relatedness using high resolution melting in a case of recurrent candiduria. BMC Microbiol. 2013 Jan 23;13:13. doi: 10.1186/1471-2180-13-13. PMID: 23343107.
PUBMED DOIHigh-Resolution Melting Analysis for Identification of the Cryptococcus neoformans-Cryptococcus gattii Complex
8. Gago S, Zaragoza Ó, Cuesta I, Rodríguez-Tudela JL, Cuenca-Estrella M, Buitrago MJ. High-resolution melting analysis for identification of the Cryptococcus neoformans-Cryptococcus gattii complex. J Clin Microbiol. 2011 Oct;49(10):3663-6. doi: 10.1128/JCM.01091-11. Epub 2011 Aug 10. PMID: 21832024.
PUBMED DOIPerformance of Panfungal- and Specific-PCR-Based Procedures for Etiological Diagnosis of Invasive Fungal Diseases on Tissue Biopsy Specimens with Proven Infection: a 7-Year Retrospective Analysis from a Reference Laboratory
9. Buitrago MJ, Bernal-Martinez L, Castelli MV, Rodriguez-Tudela JL, Cuenca-Estrella M Performance of panfungal--and specific-PCR-based procedures for etiological diagnosis of invasive fungal diseases on tissue biopsy specimens with proven infection: a 7-year retrospective analysis from a reference laboratory. J Clin Microbiol. 2014 May;52(5):1737-40. doi: 10.1128/JCM.00328-14. Epub 2014 Feb 26.PMID: 24574295.
PUBMED DOIEpidemiología actual y diagnóstico de laboratorio de las micosis endémicas en España
11. Buitrago MJ, Cuenca-Estrella M. [Current epidemiology and laboratory diagnosis of endemic mycoses in Spain]. Enferm Infecc Microbiol Clin. 2012 Aug;30(7):407-13. doi: 10.1016/j.eimc.2011.09.014. Epub 2011 Nov 29. PMID: 22130575 Review. Spanish.
PUBMED DOIA matrix-assisted laser desorption/ionization time of flight mass spectrometry reference database for the identification of Histoplasma capsulatum
12. Buitrago MJ, Bernal-Martínez L, Castelli MV, Rodríguez-Tudela JL, Cuenca-Estrella M. Histoplasmosis and paracoccidioidomycosis in a non-endemic area: a review of cases and diagnosis. J Travel Med. 2011 Jan-Feb;18(1):26-33. doi: 10.1111/j.1708-8305.2010.00477.x. Epub 2010 Nov 28. PMID: 21199139.
PUBMED DOICopy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens
13. Valero C, Buitrago MJ, Gago S, Quiles-Melero I, García-Rodríguez J. A matrix-assisted laser desorption/ionization time of flight mass spectrometry reference database for the identification of Histoplasma capsulatum. Med Mycol. 2018 Apr 1;56 (3):307-314. doi: 10.1093/mmy/myx047. PMID: 28992262.
PUBMED DOICopy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens
14. Valero C, Buitrago MJ, Gits-Muselli M, Benazra M, Sturny-Leclère A, Hamane S, Guigue N, Bretagne S, Alanio A. Copy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens. Front Microbiol. 2016 Sep 12;7:1413. doi: 10.3389/fmicb.2016.01413. eCollection 2016. PMID: 27672381.
PUBMED DOIIdentification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris
2: de Oliveira HC, Monteiro MC, Rossi SA, Pemán J, Ruiz-Gaitán A, Mendes- Giannini MJS, Mellado E, Zaragoza O. Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris. Front Cell Infect Microbiol. 2019 Apr 2;9:83. PMCID: PMC6454888.
PUBMED DOICryptococcus neoformans can form titan-like cells in vitro in response to multiple signals
Trevijano-Contador N, de Oliveira HC, García-Rodas R, Rossi SA, Llorente I, Zaballos Á, Janbon G, Ariño J, Zaragoza Ó. Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals. PLoS Pathog. 2018 May 18;14(5):e1007007. PMCID: PMC6454888.
PUBMED DOICell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host
5: Mesa-Arango AC, Rueda C, Román E, Quintin J, Terrón MC, Luque D, Netea MG, Pla J, Zaragoza O. Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2326-35. PMCID: PMC4808153.
PUBMED DOIThe production of reactive oxygen species is a universal action mechanism of Amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug
8: Mesa-Arango AC, Trevijano-Contador N, Román E, Sánchez-Fresneda R, Casas C, Herrero E, Argüelles JC, Pla J, Cuenca-Estrella M, Zaragoza O. The production of reactive oxygen species is a universal action mechanism of Amphotericin B against pathogenic yeasts and contributes to the fungicidal effect of this drug. Antimicrob Agents Chemother. 2014 Nov;58(11):6627-38. PMCID: PMC4249417.
PUBMED DOICapsule Growth in Cryptococcus neoformans Is Coordinated with Cell Cycle Progression
9: García-Rodas R, Cordero RJ, Trevijano-Contador N, Janbon G, Moyrand F, Casadevall A, Zaragoza O. Capsule growth in Cryptococcus neoformans is coordinated with cell cycle progression. mBio. 2014 Jun 17;5(3):e00945-14. PMCID: PMC4056547.
PUBMED DOIThe interaction between Candida krusei and murine macrophages results in multiple outcomes, including intracellular survival and escape from killing
12: García-Rodas R, González-Camacho F, Rodríguez-Tudela JL, Cuenca-Estrella M, Zaragoza O. The interaction between Candida krusei and murine macrophages results in multiple outcomes, including intracellular survival and escape from killing. Infect Immun. 2011 Jun;79(6):2136-44. PMCID: PMC3125833.
PUBMED DOIHuman IgM Inhibits the Formation of Titan-Like Cells in Cryptococcus neoformans
14: Trevijano-Contador N, Pianalto KM, Nichols CB, Zaragoza O, Alspaugh JA, Pirofski LA. Human IgM Inhibits the Formation of Titan-Like Cells in Cryptococcus neoformans. Infect Immun. 2020 Mar 23;88(4):e00046-20. PMCID: PMC7093138.
PUBMED DOIThe lymphocyte scavenger receptor CD5 plays a nonredundant role in fungal infection
15: Velasco-de-Andrés M, Català C, Casadó-Llombart S, Simões I, Zaragoza O, Carreras E, Lozano F. The lymphocyte scavenger receptor CD5 plays a nonredundant role in fungal infection. Cell Mol Immunol. 2020 Apr 24.
PUBMED DOIInformación adicional
1.- The study of non-gastrointestinal zoonoses, some of them transmitted by vectors and/or emerging, aims to:
- The development and validation of new diagnostic and genotyping techniques represent important scientific-technical support to the National Health System, acting as a reference laboratory.
- Research on the Molecular Epidemiology of Coxiella burnetii studies the circulating genotypes and their association with the different clinical presentations of Q fever.
- Discovery of new pathogens: especially relevant in the case of Francisella with the description of F. hispaniensis, as well as taxonomically unknown variants of Bartonella, Borrelia and Rickettsia, found in reservoirs, vectors and clinical samples.
- Surveillance in nature analyzes kinetics, transmission cycles and reservoirs.
• Genotyping techniques allow traceability studies to be carried out in the case of natural outbreaks or intentional release. • Method accreditation: ISO15189 standard (clinical samples), ISO17025 (environmental).
2.- The study of bacteria with potential use in bioterrorism through participation in European projects (Joint Actions: QUANDHIP, EMERGE, SHARP) allows us to respond appropriately to possible health alert situations. An important methodological development has been carried out for the detection of these agents and a Rapid Response System has been implemented.