Bacterial Genetics
Publications
Roles of the multiplex real-time PCR assay and β-D-glucan in a high-risk population for intra-abdominal candidiasis (IAC)
Fortún J, Buitrago MJ, Gioia F, Gómez-Gª de la Pedrosa E, Alvarez ME, Martín-Dávila P, Pintado V, Cobeta P, Martinez-Castro N, Soriano C, Moreno I, Corral S, Muñoz P, Moreno-Jimenez G, Cuenca-Estrella M, Moreno-Guillen S. Med Mycol. 2020 Aug 1;58(6):789-796.
PUBMED DOIEuropean collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants
• Avellón A, Echevarría JM, Weber B, Weik M, Schobel U, Willems WR, Gerlich WH. European collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants. J Med Virol. 2011 Jan;83(1):95-100.
PUBMED DOIPrevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain.
Prevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain. Nguyen LTT*, Román F*, Morikawa K, Trincado P, Marcos C, Rojo-Martín MD, Cafini F. Int J Antimicrob Agents. 2018 Aug;52(2):305-306.
PUBMED DOIZoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics
Rodriguez-Pastor, Ruth; Escudero, Raquel; Lambin, Xavier; Vidal, M Dolors; Gil, Horacio; Jado, Isabel; Rodriguez-Vargas, Manuela; Luque-Larena, Juan Jose; Mougeot, Francois. Zoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics. Parasitology. pp. 1 - 10. 24/09/2018.
PUBMED DOILong-range dispersal moved Francisella tularensis into Western Europe from the East
Dwibedi, Chinmay; Birdsell, Dawn; Larkeryd, Adrian; Myrtennas, Kerstin; Ohrman, Caroline; Nilsson, Elin; Karlsson, Edvin; Hochhalter, Christian; Rivera, Andrew; Maltinsky, Sara; Bayer, Brittany; Keim, Paul; Scholz, Holger C; Tomaso, Herbert; Wittwer, Matthias; Beuret, Christian; Schuerch, Nadia; Pilo, Paola; Hernandez Perez, Marta; Rodriguez-Lazaro, David; Escudero, Raquel; Anda, Pedro; Forsman, Mats; Wagner, David M; Larsson, Par; Johansson, Anders. Long-range dispersal moved Francisella tularensis into Western Europe from the East. Microbial genomics. 2 - 12, pp. e000100. 01/01/2016.
PUBMED DOIFrancisella species in ticks and animals, Iberian Peninsula
Lopes de Carvalho, I.; Toledo, A.; Carvalho, C. L.; Barandika, J. F.; Respicio-Kingry, L. B.; Garcia-Amil, C.; Garcia-Perez, A. L.; Olmeda, A. S.; Ze-Ze, L.; Petersen, J. M.; Anda, P.; Nuncio, M. S.; Escudero, R. Francisella species in ticks and animals, Iberian Peninsula. Ticks and Tick-Borne Diseases. 7 - 1, pp. 159 - 165. Elsevier GMBH, Urban & Fischer Verlag, 01/01/2016.
PUBMED DOIStable levels of Coxiella burnetii prevalence in dairy sheep flocks but changes in genotype distribution after a 10-year period in northern Spain
Álvarez-Alonso R, Barandika JF, Ruiz-Fons F, Ortega-Araiztegi I, Jado I, Hurtado A, García-Pérez AL. Stable levels of Coxiella burnetii prevalence in dairy sheep flocks but changes in genotype distribution after a 10-year period in northern Spain. Acta Vet Scand. 2018 Nov 20;60(1):75.
PUBMED DOIEvidence for Suppression of Onchocerciasis Transmission in Bioko Island, Equatorial Guinea
Moya L, Herrador Z, Ta-Tang TH, Rubio JM, Perteguer MJ, Hernandez-González A, García B, Nguema R, Nguema J, Ncog P, Garate T, Benito A, Sima A and Aparicio P. Evidence for Suppression of Onchocerciasis Transmission in Bioko Island, Equatorial Guinea.PLoS Negl Trop Dis, 2016; 10(7): e0004829.
PUBMED DOILAMP kit for diagnosis of non-falciparum malaria in Plasmodium ovale infected patients
Cuadros J, Martin Ramírez A, González IJ, Ding XC, Perez Tanoira R, Rojo-Marcos G, Gómez-Herruz P, Rubio JM. LAMP kit for diagnosis of non-falciparum malaria in Plasmodium ovale infected patients. Malar J. 2017 Jan 7;16(1):20.
PUBMED DOIPlasmodium species differentiation by non-expert on-line volunteers for remote malaria field diagnosis
Ortiz-Ruiz A, Postigo M, Gil-Casanova S, Cuadrado D, Bautista JM, Rubio JM, Luengo-Oroz M, Linares M. Plasmodium species differentiation by non-expert on-line volunteers for remote malaria field diagnosis. Malar J. 2018 Jan 30;17(1):54.
PUBMED DOIStudy of the diagnostic accuracy of microbiological techniques in the diagnosis of malaria in the immigrant population in Madrid
Martín-Díaz A, Rubio JM, Herrero-Martínez JM, Lizasoain M, Ruiz-Giardin JM, Jaqueti J, Cuadros J, Rojo-Marcos G, Martín-Rabadán P, Calderón M, Campelo C, Velasco M, Pérez-Ayala A. Study of the diagnostic accuracy of microbiological techniques in the diagnosis of malaria in the immigrant population in Madrid. Malar J. 2018 Aug 29;17(1):314.
PUBMED DOIpective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections.
Rojo-Marcos G, Rubio-Muñoz JM, Angheben A, Jaureguiberry S, García-Bujalance S, Tomasoni LR, Rodríguez-Valero N, Ruiz-Giardín JM, Salas-Coronas J, Cuadros-González J, García-Rodríguez M, Molina-Romero I, López-Vélez R, Gobbi F, Calderón-Moreno M, Martin-Echevarría E, Elía-López M, Llovo-Taboada J; TropNet Plasmodium ovale investigator group. Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections. Malar J. 2018 Oct 30;17(1):399.
PUBMED DOIImported and autochthonous malaria in West Saudi Arabia: results from a reference hospital
Soliman RH, Garcia-Aranda P, Elzagawy SM, Hussein BE, Mayah WW, Martin Ramirez A, Ta-Tang TH, Rubio JM. Imported and autochthonous malaria in West Saudi Arabia: results from a reference hospital. Malar J. 2018 Aug 7;17(1):286.
PUBMED DOICryptosporidium hominis genotypes involved in increased incidence and clusters of cases, Navarra, Spain, 2012.
Fuentes, I., Martín, C., Beristain, X; Mazón,A, Saugar, JM, Blanco, A; García M, Cenoz, Valle-Cristia, Ezpeleta, C., Castilla, J. 2015. Cryptosporidium hominis genotypes involved in increased incidence and clusters of cases, Navarra, Spain, 2012. Epidemiology and Infection; 143:1033-6
PUBMED DOIMolecular genotyping of Giardia duodenalis isolates from symptomatic individuals attending two major public hospitals in Madrid, Spain.
Lucio A, Martínez-Ruiz R, Merino FJ, Bailo B, Aguilera M, Fuentes I, Carmena D. 2015. Molecular genotyping of Giardia duodenalis isolates from symptomatic individuals attending two major public hospitals in Madrid, Spain. PLoS One. 10 (12): e0143981.
PUBMED DOIOccurrence and subtype distribution of Blastocystis sp. in humans, dogs, and cats sharing household in northern Spain and assessment of zoonotic transmission risk.
Paulos S, Köster PC, de Lucio A, Hernández-de-Mingo M, Cardona GA, Fernández-Crespo JC, Stensvold RC, Carmena D. 2018. Occurrence and subtype distribution of Blastocystis sp. in humans, dogs, and cats sharing household in northern Spain and assessment of zoonotic transmission risk. Zoonoses and Public Health, 65:993-1002.
PUBMED DOIContent with Investigacion .
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Francisco Javier Nieto Martínez
Científico titular
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Carmen Chicharro Gonzalo
Técnico Superior Especializado de OPI
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José Carlos Solana
Titulado Superior en prácticas
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Laura Botana Veguilla
Titulado Superior en prácticas
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Loren Bernardo Bernardo
Investigador predoctoral en formación
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Emilia García Diez
Ayudante de investigación
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Carmen Sánchez Herrero
Técnico superior contratado
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Raquel Budejo Sancho
Técnico superior en prácticas
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Eugenia Carrillo Gallego
Titulado Superior de Actividades Técnicas y Profesionales
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Ana Victoria Ibarra
Titulado Superior Doctor en prácticas
List of staff
Additional Information
Streptococcus pneumoniae is a human pathogen that, despite the development of vaccines, continues to be an important cause of mortality and morbidity. We investigate the mechanisms of antibiotic resistance in this bacterium. On the one hand by identifying new therapeutic targets and on the other hand by investigating the molecular basis of the action of antibiotics already used in clinical practice (the fluoroquinolones levofloxacin and moxifloxacin) or not yet used (seconeolitsine). For this purpose, we used a multidisciplinary analysis involving genomics, transcriptomics and proteomics to understand the organization of the S. pneumoniae chromosome and the identification of the factors that stabilize this organization, including ncRNAs. Changes in the level of global supercoiling, either by inhibition of gyrase (decrease) or by inhibition of topoisomerase I (increase) alter the transcriptome. The modulated genes are located in domains, whose genes show specific functional characteristics. The aim is to identify new factors essential for S. pneumoniae physiology and to characterize transcriptional regulation in response to topological stress. In addition, RNA interference technology and CRISPR systems will be used as novel antibacterials. These studies will establish the bases for translational research aimed at the development of new therapeutic targets for the treatment of pneumococcal diseases.
Streptococcus pneumoniae is a human pathogen that, despite the development of vaccines, continues to be an important cause of mortality and morbidity. We investigate the mechanisms of antibiotic resistance in this bacterium. On the one hand by identifying new therapeutic targets and on the other hand by investigating the molecular basis of the action of antibiotics already used in clinical practice (the fluoroquinolones levofloxacin and moxifloxacin) or not yet used (seconeolitsine). For this purpose, we used a multidisciplinary analysis involving genomics, transcriptomics and proteomics to understand the organization of the S. pneumoniae chromosome and the identification of the factors that stabilize this organization, including ncRNAs. Changes in the level of global supercoiling, either by inhibition of gyrase (decrease) or by inhibition of topoisomerase I (increase) alter the transcriptome. The modulated genes are located in domains, whose genes show specific functional characteristics. The aim is to identify new factors essential for S. pneumoniae physiology and to characterize transcriptional regulation in response to topological stress. In addition, RNA interference technology and CRISPR systems will be used as novel antibacterials. These studies will establish the bases for translational research aimed at the development of new therapeutic targets for the treatment of pneumococcal diseases.
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 |
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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
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Identificación capsular fenotípica y genotípica |
Aglutinación serológica en latex PCR ind/multiplex |
| | Determinación de Sensibilidad |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
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Determinación de Sensibilidad |
Microdilución Tiras epsilon Kirby Bauer |
| | Métodos fenotípicos de detección de mecanismos de resistencia |
Enterobacterias, gram-negativos no fermentadores,
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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
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ADN, PCR y secuenciación |
PCR ind/multiplex Análisis comparativo de las secuencias |
| | Tipificación molecular/análisis filogenéticos |
Haemophilus sp. Enterobacterias, gram-negativos no fermentadores, Enterococcus
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Corte enzimas de restricción, electroforesis ADN, PCR y secuenciación Preparación de librerías y secuenciación y análisis de genomas completos |
PFGE
MLST
WGS |