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Investigation
Pneumococcus
Research Lines
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Research
The Molecular Virology group focuses its research on the study of HIV-1 genetic variation and viral evolution using both in vitro and ex vivo approaches, structured around the following research lines:
- Non-progressor patients. These patients maintain control of the disease in the absence of antiretroviral therapy and have therefore been proposed as a model of functional cure. Our objective is to study the contribution of viral factors to disease control through biological characterization and analysis of viral evolution in individuals with undetectable viral loads (elite controllers, EC), compared with individuals showing other patterns of viral control.
- Viral envelope. This viral protein is key in determining viral fitness. Therefore, its functionality significantly affects infection progression. In collaboration with Dr. Blanco and Dr. Valenzuela, we study which specific events (CD4 binding, fusogenicity, etc.) are associated with envelope functionality. To this end, we have analyzed envelopes from individuals with different patterns of disease progression. Some of these have been contributed to the AIDS Research Network envelope biobank for broader use.
- Dual infection. Infection with more than one viral variant (either through co-infection or superinfection) may have consequences for infection pathogenesis. Within our group, different aspects of DI have been analyzed, including its detection in non-progressor patients, its prevalence and incidence in Spain, and its influence on the neutralizing antibody response.
- Molecular Epidemiology. The group has analyzed viral evolution throughout the epidemic in Spain and in other countries (the Netherlands, Italy, Germany, Uruguay, Panama, Brazil, etc.).
- Role of amino acid residues in reverse transcriptase. We study the role of specific amino acid residues in HIV-1 reverse transcriptase in enzymatic function and replication capacity using an infectious molecular clone previously obtained by the group.
- “In vitro” variability. Serial passage studies have been used to detect the mechanisms responsible for the gain or loss of viral fitness.
- Antiviral studies. We have analyzed the selection of resistance mutations in vitro against different antivirals, as well as the effect of these mutations on viral fitness, and the activity of new antivirals such as ATR inhibitors.
Virological Diagnosis and Reference in HIV and HTLV Infections
The research group provides diagnostic and reference activities through the service portfolio of the National Center for Microbiology to the entire Spanish National Health System.
These services include:
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Diagnosis and reference of HIV infection (types 1 and 2) through detection of specific antibodies and detection of proviral DNA by PCR.
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Diagnosis and reference of HTLV-I/II infection through detection of specific antibodies and detection of proviral DNA by PCR. Quantification of HTLV-1 proviral load by real-time PCR.
European Union Reference Laboratory (EURL) in the field of in vitro diagnostic medical devices for microbiological diagnosis (IVD) of HIV and HTLV (Regulation 2023/2713 of December 5th, 2023). Our role is to confirm the reliability and effectiveness of devices for detecting these pathogens and to ensure their specific performance requirements through laboratory testing before they can be marketed within the European Union.
Research projects
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- Towards a functional cure: Implications of early antiretroviral therapy and hormonal changes on the HIV reservoir in perinatally infected adolescents. Health Research Fund (FIS) – Carlos III Health Institute (01/01/2026 – 31/12/2028). €72,000. PI: María Pernas, Concepción Casado.
- Determination of factors associated with protection against Human Immunodeficiency Virus type 1 reinfection: Identification of correlates of protection. 9th Gilead Fellowship Program for Biomedical Research, Gilead Sciences, S.L. (01/07/2023 – 30/06/2025). €16,330. PI: María Pernas.
- Impact of the envelope on HIV viral replication: New avenues for vaccine development. Health Research Fund (FIS) – Carlos III Health Institute (01/01/2020 – 31/12/2023). €53,000. PI: María Pernas, Concepción Casado.
- Study of HIV-1 virulence in recently infected patients and its contribution, together with clinical and epidemiological factors, to disease progression. Ministry of Economy and Competitiveness. State Program for Scientific and Technical Research and Innovation (30/12/2016 – 30/06/2021). €145,000. PI: Concepción Casado, Cecilio López-Galíndez.
-Contribution of HIV-1 dual infection to virological and clinical evolution in homo/bisexual men. Health Research Fund (FIS) – Carlos III Health Institute (01/01/2014 – 31/01/2016). €74,410. PI: Cecilio López-Galíndez.
- Characterization of non-pathogenic HIV variants obtained “ex vivo” and “in vitro” for the study of disease pathogenesis. Ministry of Science and Innovation (01/01/2011 – 31/01/2014). €169,400. PI: Cecilio López-Galíndez.
- Spanish AIDS Research Network (RIS-RETIC). Carlos III Health Institute (02/01/2017 – 02/01/2022). €195,212. PI: Cecilio López-Galíndez, Concepción Casado.
Publications
Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019
Peñuelas M, Guerrero-Vadillo M, Valdezate S, Zamora MJ, Leon-Gomez I, Flores-Cuéllar Á, Carrasco G, Díaz-García O, Varela C. (2022). Botulism in Spain: Epidemiology and Outcomes of Antitoxin Treatment, 1997-2019. Toxins (Basel). 20;15(1):2
PUBMED DOIInvasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019
Villalón P, Sáez-Nieto JA, Rubio-López V, Medina-Pascual MJ, Garrido N, Carrasco G, Pino-Rosa S, Valdezate S. (2021). Invasive Streptococcus pyogenes disease in Spain: a microbiological and epidemiological study covering the period 2007-2019. Eur J Clin Microbiol Infect Dis. 2021 Nov;40(11):2295-2303
PUBMED DOIRevisiting 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 DOIHookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice.
Eichenberger RM, Ryan S, Jones L, Buitrago G, Polster R, Montes de Oca M, Zuvelek J, Giacomin PR, Dent LA, Engwerda CR, Field MA, Sotillo J, Loukas A. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front Immunol. 2018 Apr 30;9:850.
PUBMED DOIHDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans.
Flores MD, Gonzalez LM, Hurtado C, Motta YM, Domínguez-Hidalgo C, Merino FJ, Perteguer MJ, Gárate T. HDP2: a ribosomal DNA (NTS-ETS) sequence as a target for species-specific molecular diagnosis of intestinal taeniasis in humans. Parasit Vectors. 2018 Feb 27;11(1):117. doi: 10.1186/s13071-018-2646-6.
PUBMED DOIAntibody responses to chimeric peptides derived from parasite antigens in mice and other animal species.
Orbegozo-Medina RA, Martínez-Sernández V, Folgueira I, Mezo M, González-Warleta M, Perteguer MJ, Romarís F, Leiro JM, Ubeira FM. Antibody responses to chimeric peptides derived from parasite antigens in mice and other animal species. Mol Immunol. 2018 Dec 17;106:1-11.
PUBMED DOIComparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis.
Hernández-González A, Noh J, Perteguer MJ, Gárate T, Handali S. Comparison of T24H-his, GST-T24H and GST-Ts8B2 recombinant antigens in western blot, ELISA and multiplex bead-based assay for diagnosis of neurocysticercosis. Parasit Vectors. 2017 May 15;10(1):237.
PUBMED DOICharacterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication.
Eichenberger RM, Talukder MH, Field MA, Wangchuk P, Giacomin P, Loukas A, Sotillo J. Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication. J Extracell Vesicles. 2018 Jan 21;7(1):1428004.
PUBMED DOIEvaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes.
Hernández-González A, Moya L, Perteguer MJ, Herrador Z, Nguema R, Nguema J, Aparicio P, Benito A, Gárate T. Evaluation of onchocerciasis seroprevalence in Bioko Island (Equatorial Guinea) after years of disease control programmes. Parasit Vectors. 2016 Sep 20;9(1):509.
PUBMED DOIChanges in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis.
Sotillo J, Ferreira I, Potriquet J, Laha T, Navarro S, Loukas A, Mulvenna J. Changes in protein expression after treatment with Ancylostoma caninum excretory/secretory products in a mouse model of colitis. Sci Rep. 2017 Feb 13;7:41883.
PUBMED DOIFasciola 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.
PUBMED DOIAn alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains
15. Alcazar-Fuoli L, Buitrago M, Gomez-Lopez A, Mellado E. An alternative host model of a mixed fungal infection by azole susceptible and resistant Aspergillus spp strains. Virulence. 2015;6(4):376-84. doi: 10.1080/21505594.2015.1025192. PMID: 26065322.
PUBMED DOIEffect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study
Sempere J, Llamosí M, López Ruiz B, Del Río I, Pérez-García C, Lago D, Gimeno M, Coronel P, González-Camacho F, Domenech M, Yuste J. Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004-20: a national surveillance study. Lancet Microbe. 2022 Oct;3(10):e744-e752.
PUBMED DOISeconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains
Tirado-Vélez JM, Carreño D, Sevillano D, Alou L, Yuste J, de la Campa AG. Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains. Antibiotics. 2021 May 13;10(5):573.
PUBMED DOIMinilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract
Sempere J, Rossi SA, Chamorro-Herrero I, González-Camacho F, de Lucas MP, Rojas-Cabañeros JM, Taborda CP, Zaragoza Ó, Yuste J, Zambrano A. Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract. Microbiol Spectr. 2022 Jun 29;10(3):e0045322
PUBMED DOIA national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain
Sempere J, González-Camacho F, Domenech M, Llamosí M, Del Río I, López-Ruiz B, Gimeno M, Coronel P, Yuste J. A national longitudinal study evaluating the activity of cefditoren and other antibiotics against non-susceptible Streptococcus pneumoniae strains during the period 2004-20 in Spain. J Antimicrob Chemother. 2022 Mar 31;77(4):1045-1051.
PUBMED DOINationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era
de Miguel S, Domenech M, González-Camacho F, Sempere J, Vicioso D, Sanz JC, Comas LG, Ardanuy C, Fenoll A, Yuste J. Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era. Clin Infect Dis. 2021 Dec 6;73(11):e3778-e3787
PUBMED DOIPulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis
7. Mata E, Tarancón R, Guerrero C, Moreo E, Moreau F, Uranga S, Gomez AB, Marinova D, Domenech M, Gonzalez-Camacho F, Monzon M, Badiola J, Dominguez-Andres J, Yuste J, Anel A, Peixoto A, Martin C, Aguilo N. Pulmonary BCG induces lung-resident macrophage activation and confers long-term protection against tuberculosis. Sci Immunol. 2021 Sep 24;6(63):eabc2934
PUBMED DOIVaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System
Corsini B, Aguinagalde L, Ruiz S, Domenech M, Yuste J. Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System. Vaccines. 2021 Feb 23;9(2):186.
PUBMED DOIAn increase in negative supercoiling in bacteria reveals topology-reacting gene clusters and a homeostatic response mediated by the DNA topoisomerase I gene
Ferrándiz MJ, Martín-Galiano AJ, Arnanz C, Camacho-Soguero I, Tirado-Vélez JM, de la Campa AG. 2016. Nucl Acids Res. 44:7292-7303 (2016).
PUBMED DOITyrosine kinase 2 modulates splenic B cells through type I IFN and TLR7 signaling.
Bodega-Mayor I, Delgado-Wicke P, Arrabal A, Alegría-Carrasco E, Nicolao-Gómez A, Jaén-Castaño M, Espadas C, Dopazo A, Martín-Gayo E, Gaspar ML, de Andrés B, Fernández-Ruiz E. Cell Mol Life Sci. 2024 Apr 29;81(1):199.
PUBMED DOIContent with Investigacion .
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Concepción Casado Herrero
Tenure Scientist of Public Research Organizations (OPIs)
ORCID code: 0000-0003-3412-2877
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María Pernas Escario
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0003-2966-0160
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Virginia Sandonís Martín
Senior Specialized Technician of Public Research Organizations (OPIs)
ORCID code: 0000-0001-5762-7531
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Rosa Fuentes Fernández
Laboratory Technician
List of staff
Additional Information
The Pneumococcus Unit is in charge of two very important aspects related to pneumococcus infections, such as epidemiological surveillance and basic and translational research of diseases caused by this pathogen. Our unit contributes to the epidemiological surveillance of invasive pneumococcal disease (IPD), characterizing the serotypes and genotypes of invasive pneumococci circulating in Spain, as well as the evolution of antibiotic resistance in this pathogen.
Identification of culture-negative samples (CSF and pleural fluids) is performed using real-time PCR. Serotyping is performed using the Dot-blot and PCR-sequencing technique. Genotyping for the study of outbreaks and characterization of clones associated with hypervirulent and/or multiresistant strains is performed using the MLST technique and the analysis of complete genomes by massive sequencing. In addition, antibiotic susceptibility is determined following the EUCAST criteria.
Our unit belongs to the IBD-labnet network of the ECDC and annually notifies all cases of IPD to the ECDC and also to the IRIS (Invasive Respiratory Infection Surveillance) network. At the level of basic and translational research, our unit is responsible for studying and characterizing different molecular mechanisms of pathogenicity and protection related to pneumococcal infection. Among the main objectives are the molecular characterization of virulence factors, the study of different vaccine candidate proteins and determining the possible impact that tobacco smoke and the formation of biofilms have on the colonization of the respiratory tract.
The Pneumococcus Unit is in charge of two very important aspects related to pneumococcus infections, such as epidemiological surveillance and basic and translational research of diseases caused by this pathogen. Our unit contributes to the epidemiological surveillance of invasive pneumococcal disease (IPD), characterizing the serotypes and genotypes of invasive pneumococci circulating in Spain, as well as the evolution of antibiotic resistance in this pathogen.
Identification of culture-negative samples (CSF and pleural fluids) is performed using real-time PCR. Serotyping is performed using the Dot-blot and PCR-sequencing technique. Genotyping for the study of outbreaks and characterization of clones associated with hypervirulent and/or multiresistant strains is performed using the MLST technique and the analysis of complete genomes by massive sequencing. In addition, antibiotic susceptibility is determined following the EUCAST criteria.
Our unit belongs to the IBD-labnet network of the ECDC and annually notifies all cases of IPD to the ECDC and also to the IRIS (Invasive Respiratory Infection Surveillance) network. At the level of basic and translational research, our unit is responsible for studying and characterizing different molecular mechanisms of pathogenicity and protection related to pneumococcal infection. Among the main objectives are the molecular characterization of virulence factors, the study of different vaccine candidate proteins and determining the possible impact that tobacco smoke and the formation of biofilms have on the colonization of the respiratory tract.
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 |