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Investigation

Bacterial Genetics

Research Lines

Content with Investigacion Neisseria, Listeria y Bordetella .

Neisseria, Listeria y Bordetella

• Invasive Meningococcal Disease.

o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.

o Study and characterization of antimicrobial resistance mechanisms.

o Study and evaluation of conventional (polysaccharide) and new-generation (protein) vaccines.

• Gonococcal Infection (Gonorrhea).

o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.

o Study and characterization of antimicrobial resistance mechanisms.

• Listeriosis.

o Laboratory surveillance based on whole-genome sequencing and its application in Public Health.

• Pertussis.

o Development and application of molecular techniques for the diagnosis and characterization of Bordetella pertussis, B. parapertussis, B. holmessi, and B. bronchiseptica.

Research projects

Content with Investigacion Resistencia a Antibióticos e IRAS .

A continuación se detallan los proyectos de investigación del grupo con vigencia en los últimos cinco años:

1. Título del proyecto: Terapias de RNA, Inmunoterapia y Diagnóstico Avanzado frente a las Resistencias Antimicrobianas. END-RAM (PLEC2024-011123).

Proyecto financiado por el CDTI y la Agencia Estatal de Investigación en la convocatoria Transmisiones de 2024 (vigencia 2025-2028). IP: María Pérez Vázquez

2. Título del proyecto: AMIR: Inmunoterapia avanzada basada en macrófagos para infecciones resistentes a antibióticos (CPP2024-011561)

Proyecto financiado por la Agencia Estatal de Investigación en la convocatoria Retos 2025 (vigencia 2026-2028). IP: Isabela Alonso González.

3. Título del proyecto: Desarrollo y Estandarización de un Banco de fagos para el tratamiento de Infecciones Pulmonares crónicas producidas por Bacterias Multirresistentes (DEBIPhage) (COOP24CIII/00021).

Proyecto financiado por el ISCIIII en la convocatoria COOPERA-ISCIII (AESi 2024) (vigencia 2025-2028). IP: María Pérez Vázquez.

4. Título del proyecto: Estudio comprehensivo del impacto de las bacterias multirresistentes productoras de metalocarbapenemasas a nivel nacional: Proyecto multicéntrico nacional CARB/MBL-ES-25 (PI24CIII/00044)

Proyecto financiado por el ISCIII en la convocatoria AESi 2024 (vigencia 2025-2027). IPs: María Pérez Vázquez y Jesús Oteo Iglesias; coordinadora: Eva Ramírez de Arellano.

5. Título del proyecto: Phage Therapy An-persister strategy (PHAGES-An-PERS) (JPIAMR-ACTION 2024)

Proyecto financiado por la JPIAMR-Action 2024 (vigencia 2025-2027) IP: María del Mar Tomás Carmona (H.U. A Coruña). IP del CNM: Jesús Oteo Iglesias.

6. Título del proyecto: Improving surveillance of antibiotic-resistant Pseudomonas aeruginosa in Europe (ISARPAE) (JPIAMR_NC_2022-021)

Proyecto financiado por la JPI-AMR 2022 (vigencia 2023-2024) IP: Antonio Oliver Palomo (H.U Son Espases de Palma de Mallorca). Investigador del grupo en el proyecto: Jesús Oteo Iglesias.

URL: https://www.jpiamr.eu/projects/isarpae/#network-partners

7. Título del proyecto: Bridging of Antimicrobial resistance Surveillance systems In Community Settings across Europe (BASICS) (JPIAMR_NC_2022-020).

Proyecto financiado por la JPI-AMR 2022 (vigencia 2023-2024). IP: Olivier Lemenand; investigador del grupo en el proyecto: Jesús Oteo Iglesias.

URL: https://www.jpiamr.eu/projects/basics/

8. Título del proyecto: La medicina de precisión contra la resistencia a antimicrobianos: Proyecto MePRAM (PMP22/00092)

Proyecto financiado por el ISCIII en la convocatoria de Medicina Personalizada y de Precisión 2022 (vigencia 2023-junio 2026). IP: Jesús Oteo Iglesias.

9. Título del proyecto: Impact of carbapenemase-producing Klebsiella pneumoniae in patients infected by SARS-CoV-2: Prevalence and genomic characterization (PI21CIII/00039)

Proyecto financiado por el ISCIII en la convocatoria AESi 2020 (vigencia 2022-2024, prorrogado hasta 2025). IPs: María Dolores Pérez Vázquez y Jesús Oteo Iglesias.

10. Título del proyecto: Impacto de la hospitalización en UCI en el microbioma y resistoma intestinal, estudio de cohorte observacional (2018-T1/BMD-11581)

Proyecto financiado por la Dirección General de Investigación e Innovación, Consejería de Educación e Investigación de la CAM (vigencia 2019-2023). IP: Silvia García Cobos.

11. Título del proyecto: Metatranscriptomics to investigate the functional gut microbiome and resistome in critically ill patients (2022-5A/BMD-24243)

Proyecto financiado por la Dirección General de Investigación e Innovación, Consejería de Educación e Investigación de la CAM (vigencia 2023-2024). IP: Silvia García Cobos.

12. Título del proyecto: PROTECT, Inhibidores de carbapenemasas: actividad frente a Enterobacterales productores de carbapenemasas, mecanismos e impacto en la evolución de la resistencia antimicrobiana (PI22/01212).

Proyecto financiado por el ISCIII en la convocatoria AES 2022 (vigencia 2023-2025). IP: Jorge Arca Suarez. Investigador colaborador del grupo: Maria Belén Aracil.

13. Título del proyecto: Incidencia y caracterización genómica de Klebsiella pneumoniae y Escherichia coli productores de carbapenemasas aislados en hospitales españoles: Proyecto multicéntrico nacional CARB-ES-2019 (PI18CIII/00030)

Proyecto financiado por el ISCIII en la convocatoria AESi 2018 (vigencia 2019-2021, prorrogado hasta diciembre de 2022). IP: Jesús Oteo Iglesias.

14. Título del proyecto: Desarrollo preclínico de vacunas basadas en ADN plasmídico para la prevención de infecciones por Klebsiella pneumoniae y Acinetobacter baumannii multirresistente (MPY 380/18)

Proyecto financiado por el ISCIII en la convocatoria AESi 2018 (vigencia 2019-2021, prorrogado hasta diciembre de 2022). IPs: María Pérez Vázquez y Michael McConnelly

15. Aunque no se trata de proyectos de investigación con financiación competitiva al uso, caben destacar los estudios de vigilancia mediante WGS que el ECDC a través de su red EURGen-Net está llevando a cabo en los últimos años, y que se estructuran a través de redes nacionales; la subred española está coordinada desde el CNM-ISCIII por nuestro grupo.

15.1. ECDC genomic-based survey of carbapenem-resistant Acinetobacter baumannii in Europe (CRAb). Inicio 2025. Coordinación española: Belén Aracil García y Jared Sotelo Tascón

15.2. ECDC genomic surveillance of carbapenem-resistant Enterobacterales 2025 (CRE25 survey). Inicio 2025. Coordinación española Belén Aracil García y Javier Cañada García.

Financiación activa:

1. STOPINFECTIONS: Desarrollo de la primera vacuna válida internacional contra la neumonía resistente a antibióticos. Convocatoria ​Retos de Colaboración 2019. Proyecto RTC 2019-007058-1 financiado por MCIN/AEI/10.13039/501100011033.  

2. AMREADY: Desarrollo y fabricación de vacunas como soluciones y preparación ante la crisis sanitaria mundial por la resistencia a antibióticos. Convocatoria Proyectos I+D+i en líneas estratégicas, en colaboración público-privada 2021. Número de expediente PLEC2021-008078. Proyecto PLEC2021-008078 financiado por MCIN/AEI/10.13039/501100011033 y por la Unión Europea NextGenerationEU/PRTR.


 

3. TRANSVAC DS: Design Study for a European Vaccine R&D Infrastructure. (Unión Europea; Horizonte 2020) Work Package Leader: Michael McConnell. 2020-2022. 1.900.000 €.

4. Development of a multiepitope vaccine for the prevention of COVID-19. (CaixaImpulse Program) CF01-0002. IP: Michael McConnell. 2020-2020. 300.000 €.

5. NANOVAX: Desarrollo de nanopartículas funcionalizadas para mejorar la respuesta a vacunas frente a enfermedades infecciosas. (DTS19CIII/0007) Instituto de Salud Carlos III. IP: Michael McConnell. 2020-2021. 86.000 €.

6.  Desarrollo preclínico de vacunas basadas en ADN plasmídico para la prevención de infecciones por Klebsiella pneumoniae y Acinetobacter baumannii multirresistentes. Instituto de Salud Carlos III (FIS). Co-IP: Michael McConnell. 2019-2021. 97.700 €.

7. Coordinación de actividades de investigación en el CNM para realizar una respuesta integradora frente a la pandemia por SARS-COV-2 en España. Work Package Leader: Michael McConnell. 2020-2021. 325.909 €.

8. Investigación para el desarrollo de vectores de expresión de antígenos de Actinobacillus pleuropneumonia. IP: Michael McConnell. 2019-2022. 11.000 €.

9. Investigación de anticuerpos frente a Acinetobacter baumanniiCo-IP Michael McConnell. 2018-2021. 40.400 €.

10. KapaVax: Development of a trivalent vaccine for the prevention of infection caused by Acinetobacter baumanniiPseudomonas aeruginosa and Klebsiella pneumoniae. CARB-X. IP (ISCIII): Michael McConnell. 2019-2021. 89.615 €.

11. Estudio de la cinética y reactividad de los anticuerpos neutralizantes en pacientes recuperados de COVID-19. Fundación Mutua Madrileña. Work Package Leader: Michael McConnell. 2020-2021. 80.000 €.

12. STOP-Coronavirus: factores clínicos, inmunológicos, genómicos, virológicos y bioéticos de COVID-19. (ISCIII: COV20-00181). 2020-2021. 1.200.000€.

13. Desarrollo de herramientas computacionales basadas en "big data" genómico para el diagnóstico de precisión de sepsis bacteriana. (MPY 509/19). IP: Javier Martín Galiano. 2020-2022- 74,400 €.​

  En el Laboratorio de I.R.A.S., también denominado de "Infecciones Intrahospitalarias", nos centramos actualmente en la caracterización molecular de los estafilococos, tanto S. aureus, como coagulasa negativos.

   Los marcadores moleculares habituales, en el caso de los S. aureus son: electroforesis en campo pulsado (PFGE), tipificación multilocus de secuencias (MLST), tipo de casete cromosómico estafilocócico (SSCmec), tipificación spa, También detectamos, entre otros, los genes mec y PVL, los genes que codifican la Toxina exfoliativa (SST) y la Toxina del Shock Tóxico. Asimismo, para la identificación de los estafilococos coagulasa negativos, secuenciamos los genes 16S, rpoBtuf., a los que también aplicamos PFGE, SSCmec, MLST.

   Nuestras líneas de investigación se centran, por un lado, en el estudio de los mecanismos de resistencia a las oxazolidinonas: gen cfr, dominio del gen 23S ARNr , gen rplC (riboproteína L3), gen rplD (riboproteína L4), gen rplV (riboproteína L22). Hemos detectado, por primera vez, la existencia de nuevas mutaciones en la riboproteína L4 en un paciente con fibrosis quística. Aparte de los estudios llevados a cabo de las resistencias al linezolid en distintos hospitales, estudiamos en colaboración con la  Universidad de Tsukuba (Japón) y la Universidad Europea la prevalencia del plásmido pSCFS7 entre cepas cfr positivas de distintos hospitales españoles.

   Por otra parte, participamos en estudios multicéntricos (2002-2014) para conocer mejor el estado de la población estafilocócica española, centrándonos fundamentalmente en las cepas de S. aureus resistentes a meticilina (SARM); dado que es un importante patógeno humano que causa una amplia variedad de infecciones que pueden ser leves, como  algunas infecciones de piel y partes blandas, o graves, como bacteriemia, endocarditis, neumonía e infecciones de localización quirúrgica. Además, pueden producir una colonización asintomática, lo que facilita su transmisión y diseminación. Desde su descripción  inicial en 1959 y durante varias décadas, el SARM se había considerado un patógeno confinado al ámbito sanitario, pero a partir de la década de los noventa, se describe la emergencia de cepas SARM responsables de infecciones aparentemente adquiridas en la comunidad.

Dentro de esta línea estamos colaborando en el proyecto: "Colonización por S. aureus resistente a la meticilina en niños sanos de la comunidad (estudio C.O.S.A.C.O.)", que es un estudio multicéntrico de ámbito nacional.

También colaboramos con otros laboratorios en distintos estudios, como: "Mecanismos de patogenicidad y protección en bacterias Gram positivas causantes de enfermedades respiratorias y bacteriemia". 

Publications

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Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study).

5. Alastruey-Izquierdo A, Alcazar-Fuoli L, Rivero-Menéndez O, Ayats J, Castro C, García-Rodríguez J, Goterris-Bonet L, Ibáñez-Martínez E, Linares-Sicilia MJ, Martin-Gomez MT, Martín-Mazuelos E, Pelaez T, Peman J, Rezusta A, Rojo S, Tejero R, Anza DV, Viñuelas J, Zapico MS, Cuenca-Estrella M; the FILPOP2 Project from GEMICOMED (SEIMC) and REIPI. Molecular Identification and Susceptibility Testing of Molds Isolated in a Prospective Surveillance of Triazole Resistance in Spain (FILPOP2 Study). Antimicrob Agents Chemother. 2018 Aug 27;62(9).

PUBMED DOI

Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients

6. Gonçalves SM, Lagrou K, Rodrigues CS, Campos CF, Bernal-Martínez L, Rodrigues F, Silvestre R, Alcazar-Fuoli L, Maertens JA, Cunha C, Carvalho A. Evaluation of Bronchoalveolar Lavage Fluid Cytokines as Biomarkers for Invasive Pulmonary Aspergillosis in At-Risk Patients. Front Microbiol. 2017 Nov 29;8:2362.

PUBMED DOI

Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium

7. Lupiañez CB, Canet LM, Carvalho A, Alcazar-Fuoli L, Springer J, Lackner M, Segura-Catena J, Comino A, Olmedo C, Ríos R, Fernández-Montoya A, Cuenca-Estrella M, Solano C, López-Nevot MÁ, Cunha C, Oliveira-Coelho A, Villaescusa T, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Potenza L, Luppi M, Lass-Flörl C, Loeffler J, Einsele H, Vazquez L; PCRAGA Study Group, Jurado M, Sainz J. Polymorphisms in Host Immunity-Modulating Genes and Risk of Invasive Aspergillosis: Results from the AspBIOmics Consortium. Infect Immun. 2015 Dec 14;84(3):643-57.

PUBMED DOI

Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host.

9. Mesa-Arango AC, Rueda C, Román E, Quintin J, Terrón MC, Luque D, Netea MG, Pla J and 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. 60(4):2326-35.

PUBMED DOI

The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy

Benavides-Nieto M, Méndez-Echevarría A, Del Rosal T, García-García ML, Casas I, Pozo F, de la Serna O, Lopez-Granados E, Rodriguez-Pena R, Calvo C. The role of respiratory viruses in children with humoral immunodeficiency on immunoglobulin replacement therapy. Pediatr Pulmonol. 2019 Feb;54(2):194-199. Indice Impacto: 3,157. Revista en Q1.

PUBMED DOI

Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016.

Broberg EK, Waris M, Johansen K, Snacken R, Penttinen P; European Influenza Surveillance Network. Seasonality and geographical spread of respiratory syncytial virus epidemics in 15 European countries, 2010 to 2016. Euro Surveill. 2018 Feb;23(5). Indice Impacto: 5,983. Revista en Decil 1

PUBMED DOI

Human Metapneumovirus infections in hospitalized children and comparison with other respiratory viruses in 2005-2014 prospective study.

García-García ML, Calvo C, Rey C, Díaz B, Molinero MD, Pozo F, Casas I. Human Metapneumovirus infections in hospitalized children and comparison with other respiratory viruses in 2005-2014 prospective study. PLoS One. 2017 Mar 16;12(3):e0173504. doi: 10.1371/journal.pone.0173504. eCollection 2017. Indice Impacto: 2,766. Revista en Q1.

PUBMED DOI

Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children

Calvo C, Cuevas MT, Pozo F, García-García ML, Molinero M, Calderón A, Gonzalez-Esguevillas M, Pérez-Sautu U, Casas I. Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children. Pediatr Infect Dis J. 2016 Jan;35(1):45-9.

PUBMED DOI

Clinical and Virologic Characteristics of Early and Moderate Preterm Infants Readmitted with Viral Respiratory Infections.

García-Garcia ML, González-Carrasco E, Quevedo S, Muñoz C, Sánchez-Escudero V, Pozo F, Casas I, Calvo C. Clinical and Virologic Characteristics of Early and Moderate Preterm Infants Readmitted with Viral Respiratory Infections. Pediatr Infect Dis J. 2015 Jul;34(7):693-9. Indice Impacto: 2,587. Revista en Q1

PUBMED DOI

Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses.

Calvo C, García-García ML, Sanchez-Dehesa R, Román C, Tabares A, Pozo F, Casas I. Eight Year Prospective Study of Adenoviruses Infections in Hospitalized Children. Comparison with Other Respiratory Viruses. PLoS One. 2015 Jul 6;10(7):e0132162. eCollection 2015. Indice Impacto: 3,057. Revista en Q1

PUBMED DOI

Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study

Jiménez-Jorge S, Pozo F, de Mateo S, Delgado-Sanz C, Casas I, García-Cenoz M, Castilla J, Sancho R, Etxebarriarteun-Aranzabal L, Quinones C, Martínez E, Vega T, Garcia A, Giménez J, Vanrell JM, Castrillejo D, Larrauri A, on behalf of the Spanish Influenza Sentinel Surveillance System (SISS). Influenza vaccine effectiveness in Spain 2013/14: subtype-specific early estimates using the cycEVA study. Euro Surveill. 2014 Mar 6;19(9). Indice Impacto: 5,722. Revista en Q1.

PUBMED DOI

Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors

Perez-Sautu U, Pozo F, Cuesta I, Monzon S, Calderon A, Gonzalez M, Molinero M, Lopez-Miragaya I, Rey S, Cañizares A, Rodriguez G, Gonzalez-Velasco C, Lackenby A, Casas I. Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors. Euro Surveill. 2014 Jul 10;19(27):14-20. Indice Impacto: 5,722. Revista en Q1

PUBMED DOI

Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case.

Rodriguez A, Falcon A, Cuevas MT, Pozo F, Guerra S, García-Barreno B, Martinez-Orellana P, Pérez-Breña P, Montoya M, Melero JA, Pizarro M, Ortin J, Casas I, Nieto A. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case. PLoS One. 2013;8(1):e53515. doi: 10.1371/journal.pone.0053515. Epub 2013 Jan 10. Indice Impacto: 3,534. Revista en Q1

PUBMED DOI

Prospective study of influenza C in hospitalized children.

Calvo C, García-García ML, Borrell B, Pozo F, Casas I. Prospective study of influenza C in hospitalized children. Pediatr Infect Dis J. 2013 Aug;32(8):916-9. doi: 10.1097/INF.0b013e31828fca10. Indice Impacto: 3,135. Revista en Q1

PUBMED DOI

Disseminated Infection due to Mycobacterium chimaera after aortic valve replacement.

Gasch O, Meije Y, Espasa M, Font B, Jimenez MS, Fernandez-Hidalgo N. Disseminated Infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol. 2018. Jul

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Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006

3. Samper S, Gavin P, Millan-Lou MI, Iglesias M.J. Jimenez MS. Spanish Working Group on MDR-TB, Covin D, Rastogi N. Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2006. Infec Genet Evol. 2017. Aug 5;55:117.

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Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor.

5. Martinez-Hoyos M, Perez-Herran E, Gulten G, Encinas L, Alvarez-Gomez D, Alvarez E, Ferrer Bazaga S, Garcia-Perez A, Ortega F, Angulo-Bartures I, Rullas-Trincado J, Blanco Ruano D, Torres P, Castañeda P, Huss S, Fernandez R, Gonzalez del Valle S, Ballel L, Barros D, Modha S, Dhar N, Signorino-Gelo F, McKinney JD, Garcia-Bustos JF, Lavandera JL, Sacchettini JC, Jimenez MS, Martin-Casabona N, Castro-PIchel J, Mendoza-Losana A. Antitubercular drugs for an old target: GSK693 as a promising inhA direct inhibitor. EBioMedicine. 2016; 8:291-301

PUBMED DOI

Peritoneal tuberculosis due to Mycobacterium caprae.

6. Nebreda T, Alvarez-Prida E, Blanco B, Remacha MS, Samper S, Jimenez MS. Peritoneal tuberculosis due to Mycobacterium caprae. ID Cases 2016; 4:50-52.

PUBMED DOI

Pediatric drug-resistant tuberculosis in Madrid family matters

7. Santiago B, Baquero-Artiago F, Mejias A, Blázquez D, Jimenez MS, Mellado-Peña MJ, EREMITA Study group. Pediatric drug-resistant tuberculosis in Madrid: family matters. The Pediatric Infectious Disease Journal. 2014; 33:345-350.

PUBMED DOI

Mycobacterium kumamotonense, another Member of the Mycobacterium terrae Complex Unusually Carrying Two Copies of the Ribosomal RNA Operon

8. Menéndez MC, Jiménez MS, Yubero J, García MJ. Mycobacterium kumamotonense, another Member of the Mycobacterium terrae Complex Unusually Carrying Two Copies of the Ribosomal RNA Operon. Mycobac Dis; 2014; 4:176.

DOI

Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter.

9. Muñoz-Sanz A, Rodríguez Vidigal FF, Vera-Tome A, Jimenez MS. Mycobacterium mageritense meningitis in an immunocompetent patient with an intrathecal catheter. Enfer Infecc Microbiol Clin. 2013; 31:59-6

PUBMED DOI

Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain.

2. Gil H, Fernández-García A*, Mosquera MM, Hübschen JM, Castellanos AM, de Ory F, Masa-Calles J, Echevarría JE.Measles virus genotype D4 strains with non-standard length M-F non-coding region circulated during the major outbreaks of 2011-2012 in Spain. PLoS One. 2018 Jul. 16;13(7):e0199975. * Corresponding author.

PUBMED DOI

Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus

3. Banyard AC, Selden D, Wu G; Thorne L, Jennings D, Marston D, Finke S, Freuling CM, Mueller T, Echevarria JE, Fooks AR. Isolation, antigenicity and immunogenicity of Lleida Bat Lyssavirus. Journal of General Virology, 2018. 99(12):1590-1599

PUBMED DOI

Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population

6. López-Perea N, Masa-Callesa J, Torres de Miera MV, Fernández-García A, Echevarría JE, de Ory F, Martínez de Aragón MV. Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998–2014. Vaccine, 2017, 35(34): 4339-4345.

PUBMED DOI

Genetic characterization of rubella virus strains detected in Spain, 1998-2014.

8. Martínez-Torres AO, Mosquera MM, De Ory F, González-Praetorius A, Echevarría JE. Genetic characterization of rubella virus strains detected in Spain, 1998-2014. PLoS ONE. 2016. 11(9):e0162403.

PUBMED DOI

Novel Lyssavirus in bat, Spain

9. Aréchiga-Ceballos N, Vázquez-Morón S, Berciano JM, Nicolás O, Aznar- López C, Juste J, Rodríguez-Nevado C, Aguilar-Setién A, Echevarría JE. Novel Lyssavirus in bat, Spain. Emerging infectious Diseases. 2013.19(5): 793-795.

PUBMED DOI

The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years

2. Trento A, Rodriguez-Fernandez R, Gonzalez-Sanchez MI, Gonzalez-Martinez F, Mas V, Vazquez M, et al. The Complexity of Antibody Responses Elicited against the Respiratory Syncytial Virus Glycoproteins in Hospitalized Children Younger than 2 Years. Front Microbiol. 2017;8:2301.

PUBMED DOI

Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state.

3. Rossey I, Gilman MS, Kabeche SC, Sedeyn K, Wrapp D, Kanekiyo M, et al. Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state. Nat Commun. 2017;8:14158.

PUBMED DOI

Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors

6. Gilman MS, Castellanos CA, Chen M, Ngwuta JO, Goodwin E, Moin SM, et al. Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. Sci Immunol. 2016;1(6).

PUBMED DOI

Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein.

8. Gilman MS, Moin SM, Mas V, Chen M, Patel NK, Kramer K, et al. Characterization of a Prefusion-Specific Antibody That Recognizes a Quaternary, Cleavage-Dependent Epitope on the RSV Fusion Glycoprotein. PLoS Pathog. 2015;11(7):e1005035.

PUBMED DOI

Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation.

 9. Palomo C, Mas V, Vazquez M, Cano O, Luque D, Terron MC, et al. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation. Virology. 2014;460-461:119-27.

PUBMED DOI

Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus

Jiménez-Zaragoza M., Yubero M.L., Martín-Forero E., Castón J.R., Reguera D., Luque D.*, de Pablo P.J., Rodríguez J.M. 2018. Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus. eLife 7: e37295. *Corresponding author.

PUBMED DOI

Capsid structure of dsRNA fungal viruses.

Luque D., Mata C.P., Suzuki N., Ghabrial S.A., Castón J.R. 2018. Capsid structure of dsRNA fungal viruses. Viruses 10(9):481

PUBMED DOI

Structural insights into Rotavirus entry

Rodríguez J.M., Luque D.* 2019. Structural insights into Rotavirus entry. Advances in Experimental Medicine and Biology. 1215:45-68. *Corresponding author.

PUBMED DOI

Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses

Mata C.P., Luque D., Gómez-Blanco J., Rodríguez J.M., González J.M., Suzuki N., Ghabrial S.A., Carrascosa J.L., Trus B.L., Castón J.R. 2017. Acquisition of functions on the outer capsid surface during evolution of double-stranded RNA fungal viruses. PLoS Pathog. 13(12):e1006755.

PUBMED DOI

Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes

Sarker S., C. Terrón M., Khandokar Y., Aragão D., Hardy J.M., Radjainia M., Jiménez-Zaragoza M., de Pablo P.J., Coulibaly F., Luque D., Raidal D.R., Forwood J.K. 2016. Structural Insights into the Assembly and Regulation of Distinct Viral Capsid Complexes. Nat. Commun. 7:13014. IF: 12.124; D1.

PUBMED DOI

Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1

Luque D., Mata C.P., González-Camacho F., González J.M., Gómez-Blanco J., Alfonso C., Rivas G., Havens W.M., Kanematsu S., Suzuki N., Ghabrial S.A., Trus B.L., Castón J.R. 2016. Heterodimers as the structural unit of the T=1 capsid of the fungal dsRNA Rosellinia necatrix quadrivirus 1. J Virol. 90(24):11220-11230. IF: 4.666, Q1.

PUBMED DOI

Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage

Luque D., de la Escosura A., Snijder J., Brasch M., Burnley R.J, Koay M.S.T., Carrascosa J.L., Wuite G.J.L., Roos W.H., Heck A.J.R., J.J.L.M Cornelissen, Torres T., Castón J.R. 2014. Self-assembly and characterization of small and monodisperse dye nanospheres in a protein cage. Chem. Sci.,5, 575-581. IF: 9.211, D1.

DOI

Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage.

Luque D., Gómez-Blanco J., Garriga D., Brilot A.F., González J.M., Havens W.M., Carrascosa J.L., Trus B.L., Verdaguer N., Ghabrial S.A., Castón J.R. 2014. Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage. Proc Natl Acad Sci U S A 111(21):7641-7646. IF: 9.674, D1

PUBMED DOI

New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage

Rodríguez J.M., Chichón F.J., Martín-Forero E., González-Camacho F., Carrascosa J.L., Castón J.R., Luque D*. 2014. New insights into rotavirus entry machinery: stabilization of rotavirus spike conformation is independent of trypsin cleavage. PLoS Pathog. 10(5):e1004157. IF: 7.562, D1. * Corresponding autor.

PUBMED DOI

Efficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates.

3. Lameijer M, Binderup T, van Leent M, Senders M, Fay F. Seijkens T, Kroon J, Stroes E, Kjaer A, Ochando J, Reiner T, Pérez-Medina C, Calcagno C, Fischer E, Zhang B, Temel R, Swirski F, Nahrendorf M, Fayad Z, Lutgens E, Mulder W and Duivenvoorden R. Efficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates. Nature Biomedical Engineering. 2018. 2: 279–292.

PUBMED DOI

Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance.

4. Braza MS, Conde P, Garcia MR, Cortegano I, Brahmachary M, Pothula V, Fay F, Boros P, Werner SW, Ginhoux F, Mulder WJ, and Ochando J. Neutrophil derived CSF1 induces macrophage polarization and promotes transplantation tolerance. Am J Transplant. 2018.

PUBMED DOI

Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity

5. Ochando J, Conde P. Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity. J Vis Exp. 2017 Jun 7;(124). PMID: 28654060.

PUBMED DOI

The mononuclear phagocyte system in organ transplantation.

7. Ochando J, Kwan WH, Ginhoux F, Hutchinson JA, Hashimoto D, Collin M. 2015. The mononuclear phagocyte system in organ transplantation. Am J Transplant. Apr;16(4):1053-69

PUBMED DOI

Monocyte-Derived Suppressor Cells in Transplantation

8. Ochando J, Conde P, Bronte V. 2015. Monocyte-Derived Suppressor Cells in Transplantation. Curr Transplant Rep. 2015;2(2):176-183.

PUBMED DOI

DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance

9. Conde P, Rodriguez M, van der Touw W, Jimenez A, Burns M, Miller J, Brahmachary M, Chen HM, Boros P, Rausell-Palamos F, Yun TJ, Riquelme P, Rastrojo A, Aguado B, Stein-Streilein J, Tanaka M, Zhou L, Zhang J, Lowary TL, Ginhoux F, Park CG, Cheong C, Brody J, Turley SJ, Lira SA, Bronte V, Gordon S, Heeger PS, Merad M, Hutchinson J, Chen SH, Ochando J. 2015. DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance. Immunity. 16;42(6):1143-58.

PUBMED DOI

Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis

2.- Proteomic characterisation of bovine and avian purified protein derivatives and identification of specific antigens for serodiagnosis of bovine tuberculosis. Antonio Infantes-Lorenzo, Jose; Moreno, Inmaculada; Angeles Risalde, Maria; et ál. CLINICAL PROTEOMICS Volumen: 14 Número de artículo: 36 Fecha de publicación: NOV 2 2017

PUBMED DOI

Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications.

3.- Functional and structural characterization of four mouse monoclonal antibodies to complement C3 with potential therapeutic and diagnostic applications. Subias Hidalgo, Marta; Yebenes, Hugo; Rodriguez-Gallego, Cesar; et ál..EUROPEAN JOURNAL OF IMMUNOLOGY Volumen: 47 Número: 3 Páginas: 504-515 Fecha de publicación: MAR 2017

PUBMED DOI

Immunoproteomic characterisation of Mycoplasma mycoides subspecies capri by mass spectrometry analysis of two- dimensional electrophoresis spots and western blot

5.- Immunoproteomic characterisation of Mycoplasma mycoides subspecies capri by mass spectrometry analysis of two- dimensional electrophoresis spots and western blot. Churchward, Colin P.; Rosales, Ruben S.; Gielbert, Adriana; et ál..JOURNAL OF PHARMACY AND PHARMACOLOGY Volumen: 67 Número: 3 Número especial: SI Páginas: 364-371 Fecha de publicación: MAR 2015

PUBMED DOI

Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis.

6.- Efficacy of low doses of amphotericin B plus allicin against experimental visceral leishmaniasis. Corral, M. Jesus; Serrano, Dolores R.; Moreno, Inmaculada; et ál..JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Volumen: 69 Número: 12 Páginas: 3268-3274 Fecha de publicación: DEC 2014

PUBMED DOI

A Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models

7.- A Novel Antibody against Human Factor B that Blocks Formation of the C3bB Proconvertase and Inhibits Complement Activation in Disease Models. Subias, Marta; Tortajada, Agustin; Gastoldi, Sara; et ál..JOURNAL OF IMMUNOLOGY Volumen: 193 Número: 11 Páginas: 5567-5575 Fecha de publicación: DEC 2014

PUBMED DOI

Detection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test

8.- Detection of anti-Leishmania infantum antibodies in sylvatic lagomorphs from an epidemic area of Madrid using the indirect immunofluorescence antibody test. Moreno, Inmaculada; Alvarez, Julio; Garcia, Nerea; et ál..VETERINARY PARASITOLOGY Volumen: 199 Número: 3-4 Páginas: 264-267 Fecha de publicación: 2014

PUBMED DOI

Evidence of Leishmania infantum Infection in Rabbits (Oryctolagus cuniculus) in a Natural Area in Madrid, Spain.

9.- Evidence of Leishmania infantum Infection in Rabbits (Oryctolagus cuniculus) in a Natural Area in Madrid, Spain. Garcia, Nerea; Moreno, Inmaculada; Alvarez, Julio; et ál..BIOMED RESEARCH INTERNATIONAL Número de artículo: 318254 Fecha de publicación: 2014

PUBMED DOI

Mucus-Activatable Shiga Toxin Genotype stx2d in Escherichia coli O157:H7

2. Sánchez, S., Llorente, M.T., Herrera-León, L., Ramiro, R., Nebreda, S., Remacha, M.A., Herrera-León, S. Mucus-activatable shiga toxin genotype stx2d in Escherichia coli O157:H7. (2017) Emerging Infectious Diseases, 23 (8), pp. 1431-1433.

PUBMED DOI

Multinational outbreak of travel-related Salmonella Chester infections in europe, summers 2014 and 2015

3. Fonteneau, L., Da Silva, N.J., Fabre, L., Ashton, P., Torpdahl, M., Müller, L., Bouchrif, B., El Boulani, A., Valkanou, E., Mattheus, W., Friesema, I., Herrera Leon, S., Varela Martínez, C., Mossong, J., Severi, E., Grant, K., Weill, F., Gossner, C.M., Bertrand, S., Dallman, T., Le Hello, S. Multinational outbreak of travel-related Salmonella Chester infections in europe, summers 2014 and 2015. (2017) Eurosurveillance, 22 (7).

PUBMED DOI

Prospective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis

4. Inns, T., Ashton, P.M., Herrera-Leon, S., Lighthill, J., Foulkes, S., Jombart, T., Rehman, Y., Fox, A., Dallman, T., De Pinna, E., Browning, L., Coia, J.E., Edeghere, O., Vivancos, R. Prospective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis (2017) Epidemiology and Infection, 145 (2), pp. 289-298.

PUBMED DOI

Plasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler's diarrhea cases.

5. Herrera-Leon, S., Llorente, M.T., Sanchez, S. Plasmid-mediated quinolone resistance in different diarrheagenic Escherichia coli pathotypes responsible for complicated, noncomplicated, and traveler's diarrhea cases. (2016) Antimicrobial Agents and Chemotherapy, 60 (3), pp. 1950-1951.

PUBMED DOI

Molecular Epidemiology and Antibiotic Susceptibility of Vibrio cholerae Associated with a Large Cholera Outbreak in Ghana in 2014.

6. Eibach, D., Herrera-León, S., Gil, H., Hogan, B., Ehlkes, L., Adjabeng, M., Kreuels, B., Nagel, M., Opare, D., Fobil, J.N., May, J. Molecular Epidemiology and Antibiotic Susceptibility of Vibrio cholerae Associated with a Large Cholera Outbreak in Ghana in 2014. (2016) PLoS Neglected Tropical Diseases, 10 (5).

PUBMED DOI

What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B

7. Connor, T.R., Owen, S.V., Langridge, G., Connell, S., Nair, S., Reuter, S., Dallman, T.J., Corander, J., Tabing, K.C., Le Hello, S., Fookes, M., Doublet, B., Zhou, Z., Feltwell, T., Ellington, M.J., Herrera, S., Gilmour, M., Cloeckaert, A., Achtman, M., Parkhill, J., Wain, J., De Pinna, E., Weill, F.-X., Peters, T., Thomson, N. What’s in a name? Species-wide whole-genome sequencing resolves invasive and noninvasive lineages of Salmonella enterica serotype Paratyphi B (2016) mBio, 7 (4).

PUBMED DOI

Invasive salmonella infections among children from Rural Mozambique, 2001-2014

9. Mandomando, I., Bassat, Q., Sigaúque, B., Massora, S., Quintó, L., Ácacio, S., Nhampossa, T., Vubil, D., Garrine, M., Macete, E., Aide, P., Sacoor, C., Herrera-León, S., Ruiz, J., Tennant, S.M., Menéndez, C., Alonso, P.L. Invasive salmonella infections among children from Rural Mozambique, 2001-2014 (2015) Clinical Infectious Diseases, 61, pp. S339-S345.

PUBMED DOI

Content with Investigacion Resistencia a Antibióticos e IRAS .

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.

Content with Investigacion Taxonomía Bacteriana .