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Investigation

Antibiotic Resistance

Research Lines

Content with Investigacion Taxonomía Bacteriana .

Taxonomía Bacteriana

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Research projects

Content with Investigacion Taxonomía Bacteriana .

- Título: Desvelando la genómica de las bacterias anaerobias procedentes de bacteriemias
Referencia Proyecto: PID202-1127477OB-I00-MPY 302/22.
Entidad financiador: Agencia Estatal de Investigación.
Fechas de ejecución: 2023-2026
Financiación 108.900 €.
Investigadora principal: Sylvia Valdezate


 

- Título: Plataformas MALDI-TOF/CMI SENSITITRETM Personal Técnico Apoyo
Referencia: PTA2019-016623-I. 
Entidad Financiadora: Agencia Estatal de Investigación. 
Fechas ejecución 12/2020-11/2023
Investigadora principal: Sylvia Valdezate

- Título: Elementos genéticos móviles protagonistas en la evolución de los serotipos pandémicos M1 y M89 de Streptococcus pyogenes en el síndrome del shock tóxico y otras infecciones invasivas
Referencia: (MPY 377/18).
Entidad financiadora: Instituto de Salud Carlos III. Agencia Estatal de Investigación en Salud Intramural (AESI). 
Fechas de ejecución: 11/2018-12/2022. 
Financiación: 40.000 €.
Investigadoras principales: Pilar Villalón. Co-IP Sylvia Valdezate. 

- Título: Plataformas genéticas y su influencia en la resistencia a co-trimoxazol, macrólidos y tetraciclina en Nocardia spp.
Referencia: MPY 1278/15
Entidad financiadora: Instituto de Salud Carlos III. Agencia Estatal de Investigación en Salud Intramural (AESI).
Fechas de ejecución: 2015-2017.
Financiación: 88.141,8 €. 
Investigadora principal: Sylvia Valdezate

- Título: Filogenia y caracterización de mecanismos moleculares de resistencia en Nocardia spp. 
Referencia: MPY 1446/11
Entidad financiadora: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria (AES). () 
Fechas de ejecución: 04/2012-10/2015
Financiación: 115.457 €. 
Investigadora principal: Sylvia Valdezate.

- Título: Iberian network of laboratories of biological alert. Accreditation of methods for detection highly pathogenic agents (IB-BIOALERTNET). 
Entidad financiadora: COMISIÓN EUROPEA HOME/2012/ISEC/AG/CBRN/4000003810. (Instituto de Salud Carlos III (VISAVET, IVIA, INSA, INIAV))
Referencia: SAFI 1132/13-7. 
Fecha de ejecución: 2013-2015.
Financiación: 699.175 €. 
Tipo de participación: Miembro del equipo investigador.

- Título: EQUATOX Project Establishment of Quality Assurances for theDetection of Biological Toxins of potential Bioterrorism risk. 
Entidad financiadora y convocatoria: Seven Framework Programme for Research FP7-SECURITY. (Robert Koch-Institut Berlin Alemania). 
Referencia: SEC-2011.5.4-1. 
Fechas de ejecución: 2012-2014.

Publications

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Immunoinformatics lessons on the current COVID-19 pandemic and future coronavirus zoonoses

López D, García-Peydró M. “Immunoinformatics lessons on the current COVID-19 pandemic and future coronavirus zoonoses”. Frontiers in Immunology 14:1118267 (2023).

PUBMED DOI

Predicted HLA Class I and Class II Epitopes From Licensed Vaccines Are Largely Conserved in New SARS-CoV-2 Omicron Variant of Concern.

López, D. 2022. Predicted HLA Class I and Class II Epitopes From Licensed Vaccines Are Largely Conserved in New SARS-CoV-2 Omicron Variant of Concern. Front Immunol. 13:832889.

PUBMED

Garcia-Arriaza, J., M. Esteban, and D. López. 2021

Garcia-Arriaza, J., M. Esteban, and D. López. 2021. Modified Vaccinia Virus Ankara as a Viral Vector for Vaccine Candidates against Chikungunya Virus. Biomedicines. 9.

PUBMED

Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins

Tajuelo, A., M. López-Siles, V. Mas, P. Perez-Romero, J. M. Aguado, V. Briz, M. J. McConnell, A. J. Martín-Galiano, and D. López. 2022. Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins. Int.J.Mol.Sci. 23.

PUBMED

Abundance, Betweenness Centrality, Hydrophobicity, and Isoelectric Points Are Relevant Factors in the Processing of Parental Proteins of the HLA Class II Ligandome.

Lorente, E., A. J. Martín-Galiano, D. M. Kadosh, A. Barriga, J. Garcia-Arriaza, C. Mir, M. Esteban, A. Admon, and D. López. 2022. Abundance, Betweenness Centrality, Hydrophobicity, and Isoelectric Points Are Relevant Factors in the Processing of Parental Proteins of the HLA Class II Ligandome. J.Proteome.Res. 21:164-171.

DOI

Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1.

López, D. 2022. Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1. Biomedicines. 10.

PUBMED DOI

Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern.

Martín-Galiano, A. J., F. Diez-Fuertes, M. J. McConnell, and D. López. 2021. Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern. Front Immunol. 12:732693.

PUBMED DOI

de la Sota, P. G., E. Lorente, L. Notario, C. Mir, O. Zaragoza, and D. López. 2021. Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus. Biomedicines. 9.

de la Sota, P. G., E. Lorente, L. Notario, C. Mir, O. Zaragoza, and D. López. 2021. Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus. Biomedicines. 9.

PUBMED DOI

Lorente, E., M. Marcilla, P. G. de la Sota, A. Quijada-Freire, C. Mir, and D. López. 2021. Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry. Int.J.Mol.Sci. 22.

Lorente, E., M. Marcilla, P. G. de la Sota, A. Quijada-Freire, C. Mir, and D. López. 2021. Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry. Int.J.Mol.Sci. 22.

PUBMED DOI

Redondo-Anton, J., M. G. Fontela, L. Notario, R. Torres-Ruiz, S. Rodriguez-Perales, E. Lorente, and P. Lauzurica. 2020. Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression. Front Genet. 11:552949.

Redondo-Anton, J., M. G. Fontela, L. Notario, R. Torres-Ruiz, S. Rodriguez-Perales, E. Lorente, and P. Lauzurica. 2020. Functional Characterization of a Dual Enhancer/Promoter Regulatory Element Leading Human CD69 Expression. Front Genet. 11:552949.

PUBMED DOI

Lorente, E., E. Barnea, C. Mir, A. Admon, and D. López. 2020. The HLA-DP peptide repertoire from human respiratory syncytial virus is focused on major structural proteins with the exception of the viral polymerase. J Proteomics. 221:103759.

Lorente, E., E. Barnea, C. Mir, A. Admon, and D. López. 2020. The HLA-DP peptide repertoire from human respiratory syncytial virus is focused on major structural proteins with the exception of the viral polymerase. J Proteomics. 221:103759.

PUBMED DOI

Lorente, E., M. G. Fontela, E. Barnea, A. J. Martín-Galiano, C. Mir, B. Galocha, A. Admon, P. Lauzurica, and D. López. 2020. Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2). Mol.Cell Proteomics. 19:994-1004.

Lorente, E., M. G. Fontela, E. Barnea, A. J. Martín-Galiano, C. Mir, B. Galocha, A. Admon, P. Lauzurica, and D. López. 2020. Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2). Mol.Cell Proteomics. 19:994-1004.

PUBMED DOI

Marquez, A., M. Gomez-Fontela, S. Lauzurica, R. Candorcio-Simon, D. Munoz-Martín, M. Morales, M. Ubago, C. Toledo, P. Lauzurica, and C. Molpeceres. 2020. Fluorescence enhanced BA-LIFT for single cell detection and isolation. Biofabrication. 12:025019.

Marquez, A., M. Gomez-Fontela, S. Lauzurica, R. Candorcio-Simon, D. Munoz-Martín, M. Morales, M. Ubago, C. Toledo, P. Lauzurica, and C. Molpeceres. 2020. Fluorescence enhanced BA-LIFT for single cell detection and isolation. Biofabrication. 12:025019.

PUBMED DOI

Lorente, E., C. Palomo, E. Barnea, C. Mir, V. M. Del, A. Admon, and D. López. 2019a. Natural Spleen Cell Ligandome in Transporter Antigen Processing-Deficient Mice. J.Proteome.Res. 18:3512-3520.

Lorente, E., C. Palomo, E. Barnea, C. Mir, V. M. Del, A. Admon, and D. López. 2019a. Natural Spleen Cell Ligandome in Transporter Antigen Processing-Deficient Mice. J.Proteome.Res. 18:3512-3520.

PUBMED

Lorente, E., J. Redondo-Anton, A. Martín-Esteban, P. Guasp, E. Barnea, P. Lauzurica, A. Admon, and J. A. López de Castro. 2019. Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis. Mol.Cell Proteomics. 18:2298-2309.

Lorente, E., J. Redondo-Anton, A. Martín-Esteban, P. Guasp, E. Barnea, P. Lauzurica, A. Admon, and J. A. López de Castro. 2019. Substantial Influence of ERAP2 on the HLA-B*40:02 Peptidome: Implications for HLA-B*27-Negative Ankylosing Spondylitis. Mol.Cell Proteomics. 18:2298-2309.

PUBMED DOI

Brait, V. H., F. Miro-Mur, I. Perez-de-Puig, L. Notario, B. Hurtado, J. Pedragosa, M. Gallizioli, F. Jimenez-Altayo, M. Arbaizar-Rovirosa, A. Otxoa-de-Amezaga, J. Monteagudo, M. Ferrer-Ferrer, l. R. de, X, E. Bonfill-Teixidor, A. Salas-Perdomo, A. Hernandez-Vidal, P. Garcia-de-Frutos, P. Lauzurica, and A. M. Planas. 2019. CD69 Plays a Beneficial Role in Ischemic Stroke by Dampening Endothelial Activation. Circ.Res. 124:279-291.

Brait, V. H., F. Miro-Mur, I. Perez-de-Puig, L. Notario, B. Hurtado, J. Pedragosa, M. Gallizioli, F. Jimenez-Altayo, M. Arbaizar-Rovirosa, A. Otxoa-de-Amezaga, J. Monteagudo, M. Ferrer-Ferrer, l. R. de, X, E. Bonfill-Teixidor, A. Salas-Perdomo, A. Hernandez-Vidal, P. Garcia-de-Frutos, P. Lauzurica, and A. M. Planas. 2019. CD69 Plays a Beneficial Role in Ischemic Stroke by Dampening Endothelial Activation. Circ.Res. 124:279-291.

DOI

López, D., A. Barriga, E. Lorente, and C. Mir. 2019. Immunoproteomic Lessons for Human Respiratory Syncytial Virus Vaccine Design. J.Clin.Med. 8.

López, D., A. Barriga, E. Lorente, and C. Mir. 2019. Immunoproteomic Lessons for Human Respiratory Syncytial Virus Vaccine Design. J.Clin.Med. 8.

PUBMED DOI

Lorente, E., A. Barriga, E. Barnea, C. Palomo, J. Garcia-Arriaza, C. Mir, M. Esteban, A. Admon, and D. López. 2019. Immunoproteomic analysis of a Chikungunya poxvirus-based vaccine reveals high HLA class II immunoprevalence. PLoS.Negl.Trop.Dis. 13:e0007547.

Lorente, E., A. Barriga, E. Barnea, C. Palomo, J. Garcia-Arriaza, C. Mir, M. Esteban, A. Admon, and D. López. 2019. Immunoproteomic analysis of a Chikungunya poxvirus-based vaccine reveals high HLA class II immunoprevalence. PLoS.Negl.Trop.Dis. 13:e0007547.

PUBMED DOI

Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells.

Martin-Galiano, A. J. and Lopez, D. (2019) Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells. PLoS.ONE. 14, e0210583.

PUBMED DOI

Proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for HLA class II ligands in vaccinia virus-infected cells.

Lorente, E., Martin-Galiano, A. J., Barnea, E., Barriga, A., Palomo, C., Garcia-Arriaza, J., Mir, C., Lauzurica, P., Esteban, M., Admon, A., and Lopez, D. (2019) Proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for HLA class II ligands in vaccinia virus-infected cells. J.Proteome.Res. 18(9):3512-3520

PUBMED DOI

List of staff

Additional Information

Our general objective is to provide early knowledge about any emerging antibiotic resistance mechanism in our country. This contribution of knowledge is based on transversal objectives that we consider key, such as 1) the ability to adapt research to emerging resistance problems, 2) the promotion of cooperative and multidisciplinary research studies working in networks with different Spanish and foreign centers, 3) the transfer of research results in an agile way to the clinical practice of the national health system, and 4) the promotion of the interrelation of research with reference, advice, training and dissemination seeking the empowerment of all. 

More specifically, our main scientific objectives are the characterization of the molecular bases of antibiotic resistance in pathogenic bacteria, the study of the molecular epidemiology and population structure of resistant bacteria, the characterization of the mobile genetic elements that carry resistance genes, and the development of diagnostic techniques and therapeutic alternatives against bacteria with extensive resistance to antibiotics. In this sense, research into the dissemination pathways of Enterobacteriaceae, Acinetobacter baumannii and carbapenemase-producing Pseudomonas aeruginosa (as a paradigm of extensive resistance and pan-resistance) is one of our current priority objectives.

Our general objective is to provide early knowledge about any emerging antibiotic resistance mechanism in our country. This contribution of knowledge is based on transversal objectives that we consider key, such as 1) the ability to adapt research to emerging resistance problems, 2) the promotion of cooperative and multidisciplinary research studies working in networks with different Spanish and foreign centers, 3) the transfer of research results in an agile way to the clinical practice of the national health system, and 4) the promotion of the interrelation of research with reference, advice, training and dissemination seeking the empowerment of all. 

More specifically, our main scientific objectives are the characterization of the molecular bases of antibiotic resistance in pathogenic bacteria, the study of the molecular epidemiology and population structure of resistant bacteria, the characterization of the mobile genetic elements that carry resistance genes, and the development of diagnostic techniques and therapeutic alternatives against bacteria with extensive resistance to antibiotics. In this sense, research into the dissemination pathways of Enterobacteriaceae, Acinetobacter baumannii and carbapenemase-producing Pseudomonas aeruginosa (as a paradigm of extensive resistance and pan-resistance) is one of our current priority objectives.

The current director of CNM is Dr. José Miguel Rubio Muñoz.

Dr. José Miguel Rubio has a degree in Biological Sciences from the Universidad Autónoma de Madrid (1986) and a PhD in Biological Sciences from the same university (1992). He carried out his doctoral thesis at the Department of Genetics of the Universidad Autónoma de Madrid, as Associate Professor (1988-1989), and at the School of Biology of the University of East Anglia in Norwich, UK, as Senior Research Assistant (1989-1992).

During his postdoctoral period he obtained a grant from the European Commission within the Human Capital and Mobility Program to be carried out at the University of “La Sapienza” in Rome, Italy and the Institute of Molecular Biology and Biotechnology in Crete, Greece (1993-1994). Subsequently, he made a further stay funded by the WHO and the university itself at the Department of Entomology, Wageningen University, The Netherlands (1994-1996).

Since 1997 he has been a member of the Instituto de Salud Carlos III (ISCIII), where he joined the Department of Parasitology of the National Center of Microbiology, as an EU-INCO postdoctoral fellow and later with a grant from the Autonomous Community of Madrid (CAM). She was part of the founding group of the National Center for Tropical Medicine (2003-2006) and of the 24/7 Alerts and Emergencies Unit (2006-2018) and is currently Head of the Malaria and Emerging Parasitosis Unit of the National Microbiology Center and is part, as research staff, of the Center for Biomedical Research Network on Infectious Diseases (CIBERINFEC/ISCIII).

During his scientific career he has been Visiting Scientist at the Leonidas e Marie Dean Center (FIOCRUZ-AMAZONAS, Manaus, Brazil) and is an External Consultant of the Parasitology Departments of Cairo University (Egypt) and the Medical Research Center (MRC) of Kuala Lumpur (Malaysia).  He also belongs or has belonged to different national and international committees:  Member of the expert group for malaria control of the European Centre for Disease Control (ECDC) since 2011; Expert-Evaluator for health programs of the European Commission since 2004; Spanish Representative (commissioned by ISCIII and MSC) in the Technical Scientific Committee of the TDR (WHO) 2007-2008; Spanish Deputy Focal Point for microbiology at the European Centre for Disease Control (ECDC) from 2012 to 2020; and, member of the Research Ethics Committee of ISCIII until 2019.

In this period he has published more than 100 articles in international indexed journals, 10 book chapters and has been co-editor of two books in the area of malaria, tropical medicine and neglected diseases. He has participated in 58 competitively funded research projects, 20 of them international, having been the principal investigator in 8 national and 11 international projects as PI of the project or WP leader. In addition, he has led five agreements with companies. Currently he has been awarded four sexenios of research, being presented this year 2025 to the fifth. In the teaching field, he participates in different postgraduate programs in the areas of microbiology and parasitology, having directed seven doctoral theses and more than 20 Master's or Degree final projects, both nationally and internationally. ​​​​​

El laboratorio de Referencia e Investigación en Resistencia a Antibióticos ofrece una amplia cartera de servicios al Sistema Nacional de Salud, las cuales pueden solicitarse en cnm-laboratorios.isciii.es. Jefe del Laboratorio: Jesús Oteo Iglesias (Punto focal Nacional de Resistencia antibiótica).

Dispone de dos programas de Vigilancia oficiales y gratuitos que engloban los ensayos ofertados ya sea como aislamientos individuales o mediante estudio de brotes. El Laboratorio utiliza asimismo técnicas de PCR en tiempo real para la detección de genes de resistencia, estas técnicas se han adaptado a un formato multiplex que permite detectar varios genes en la misma reacción. En los últimos años se han incluido metodologías basadas en la secuenciación de genomas completos para el análisis de bacterias multiresistentes (WGS).

Programa de vigilancia de Haemophilus influenzae. Responsables: María Pérez Vázquez (Punto focal Nacional de Haemophilus influenzae) y Belén Aracil. Laboratorio encargado de la identificación, estudio de sensibilidad y análisis genotípico de aislados de Haemophilus influenzae, centrándose esencialmente en la patología invasiva debida este patógeno. 

Programa de vigilancia de Resistencia a Antibióticos. Responsables: María Pérez Vázquez  y Belén Aracil (Punto focal Nacional de Resistencia antibiótica). Laboratorio encargado de la identificación, el estudio de sensibilidad antibiótica, y el diagnóstico fenotípico y genotípico de los diferentes mecanismos de resistencia a antibióticos fundamentalmente en enterobacterias y gram-negativos no fermentadores y Enterococcus spp.

Estudio de brotes. Responsables: Belén Aracil y María Pérez Vázquez. El programa incluye la caracterización de brotes nosocomiales y clones emergentes de alto riesgo mediante diferentes técnicas moleculares (tabla resumen). Éstas, nos permiten realizar estudios filogenéticos con el fin de obtener una información detallada acerca la relación entre los diferentes aislados y su trazabilidad. El objetivo final es generar datos que se transfieren a los hospitales como ayuda para la prevención o control de la propagación del brote.

Acreditación y Calidad. Responsable: Belén Aracil. El laboratorio Referencia e Investigación en Resistencia a Antibióticos ha sido de los primeros en el ISCIII en la utilización de técnicas acreditadas por la Entidad Nacional de Acreditaciones (ENAC). Este laboratorio consiguió la primera acreditación homologada de técnicas diagnósticas en 2012, programa que ha sido ampliado, de manera que en la actualidad más de la mitad de las técnicas ofrecidas al Sistema Nacional de Salud están debidamente acreditadas por ENAC.

Técnicos responsables de las técnicas realizadas en el Laboratorio: Noelia Lara Fuella y Verónica Bautista Sánchez.

En la siguiente imagen se resumen las técnicas ofrecidas al Sistema Nacional de Salud.

PROGRAMAS NOMBRE CARTERA SERVICIO PATÓGENO DETERMINACIÓN, DETECCIÓN, ANÁLISIS MÉTODOS

Programa de vigilancia de Haemophilus

Programa de vigilancia de resistencia a antibióticos.

Identificación bacteriana

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus spp

Identificación bacteriana

Bioquímicos

MALDI TOF

Secuenciación de RNAr

Identificación capsular

Haemophilus influenzae

 

Identificación capsular fenotípica y genotípica

Aglutinación serológica en latex

PCR ind/multiplex

Determinación de Sensibilidad

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

Determinación de Sensibilidad

Microdilución                

Tiras epsilon               

Kirby Bauer

Métodos fenotípicos de detección de mecanismos de resistencia

Enterobacterias, gram-negativos no fermentadores,

 

Métodos fenotípicos de detección de mecanismos de resistencia

Discos y tabletas combinados con inhibidores                

Tiras combinadas     

Test de Hodge modificado

CabaNP                               

Inmunocromatografía CBP

Métodos genotípicos de detección de mecanismos de resistencia

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

ADN, PCR y secuenciación

PCR ind/multiplex

Análisis comparativo de las secuencias

Tipificación molecular/análisis filogenéticos

Haemophilus sp.

Enterobacterias, gram-negativos no fermentadores, Enterococcus

 

Corte enzimas de restricción, electroforesis

ADN, PCR y secuenciación

Preparación de librerías y secuenciación y análisis de genomas completos

 

PFGE

 

MLST

 

WGS