Bacterial Genetics
Líneas de investigación
Content with Investigacion .
Bacterial Genetics
Our group has been studying for more than 30 years the mechanisms of antibiotic resistance in Streptococcus pneumoniae (Spn). Our objectives are to understand the molecular basis of antimicrobial action, to search for new targets of action and new compounds. Seconeolitsine (SCN) is one of these new compounds targeting topoisomerase I (Topo I). As for the search for new targets, our research has focused in recent years on the factors that organize the topology of the chromosome, allowing optimal compaction (about 1000-fold) to harmonize its replication, chromosome segregation and gene expression. This compaction is mediated both by the level of DNA supercoiling (Sc) and by association with nucleoid-binding proteins (NAPs). The level of Sc depends mainly on the enzymatic activities of their DNA topoisomerases, reaching a homeostatic equilibrium by the opposite activities of the topoisomerases that relax DNA (Topo I and Topo IV), and of gyrase, which introduces negative Sc. Our group has characterized the three Spn topoisomerases and two NAPs: HU and SatR. In addition, the availability of antimicrobials that inhibit each of the Spn topoisomerases has allowed us to analyze their transcriptome under conditions of local or global change of the Sc level and to define gene domains of coordinated transcription and similar functions. Fluoroquinolones, which inhibit Topo IV and gyrase, produce local changes in Sc that induce alterations in 6% of the transcriptome, altering metabolic pathways that originate an increase in reactive oxygen species (ROS) that contribute to lethality, in accordance with the general mechanism of bactericidal antibiotics. On the other hand, the induction of global changes in Sc by novobiocin (NOV, gyrase inhibitor), or by SCN (Topo I inhibitor), has allowed us to define topological domains. Global changes in Sc include the regulation of topoisomerase genes: its decrease activates the transcription of gyrase genes (gyrA, gyrB) and inhibits those of Topo IV (parEC) and Topo I (topA); the increase in Sc regulates the expression of topA. Decreased Sc affects 37% of the genome, with >68% of genes clustered in 15 domains. Increased Sc affects 10% of the genome, with 25% of the genes clustered in 12 domains. The AT content in the genome correlates with the domains, being higher in UP domains than in DOWN domains. The genes in the different domains have common functional characteristics, indicating that they have been subjected to topological selective pressure to determine the location of genes involved in metabolism, virulence and competition.
The current objectives of the group are:
1. Identification of factors that stabilize chromosome topology: NAPs, ncRNAs, intra-chromosomal interactions.
2. Regulation of transcription in response to topological stress: in vivo localization of DNA topoisomerases, RNA polymerase and NAPs.
3. Topo I as a new antimicrobial target and action of SCN.
4. Design of antisense RNAs and use of the CRISPR system as new antibacterial agents.
Proyectos de investigación
Content with Investigacion .
1) Project Title: Interaction Between DNA Supercoiling and Transcription in the Human Pathogen Streptococcus pneumoniae.
Principal Investigator: Adela González de la Campa
Funding Entity: Ministry of Science and Innovation, State Research Agency (Call for "R&D&I Projects" 2020 – "Research Challenges" and "Knowledge Generation" Modalities).
Reference: PID2021-124738OB-100.
Duration: 2022-2025.
Funding Amount: €108,900.
2) Project Title: Study of the Factors Organizing the Chromosome of Streptococcus pneumoniae: New Antibiotic Targets and Resistance Mechanisms.
Principal Investigator: Adela González de la Campa
Funding Entity: Ministry of Economy, Industry, and Competitiveness. State Research Agency.
Reference: BIO2017-82951-R.
Duration: 2018-2020.
Funding Amount: €169,400.
3) Project Title: Role of DNA Topoisomerases and Nucleoid-Associated Proteins in the Chromosome Organization of Streptococcus pneumoniae: Response to Antibiotics and Virulence.
Principal Investigator: Adela González de la Campa
Funding Entity: Ministry of Economy and Competitiveness. Secretariat of State for Research, Development, and Innovation.
Reference: BIO2014-55462.
Duration: 2015-2017.
Funding Amount: €193,600.
4) Project Title: The Control of Supercoiling Level in Streptococcus pneumoniae as an Antimicrobial Target.
Principal Investigator: Adela González de la Campa
Funding Entity: Ministry of Economy and Competitiveness. Secretariat of State for Research, Development, and Innovation.
Reference: BIO2011-25343.
Duration: 2012-2015.
Funding Amount: €209,000.
5) Project Title: Role of Small Non-Coding RNAs in the Pathogenicity of Streptococcus pneumoniae.
Principal Investigator: Mónica Amblar Esteban
Funding Entity: Ministry of Economy and Competitiveness. Strategic Health Action (AES).
Reference: PI11/00656.
Duration: 2012-2015.
Funding Amount: €198,714.
Publicaciones destacadas
Lupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23
Lupiañez CB, Martínez-Bueno M, Sánchez-Maldonado JM, Badiola J, Cunha C, Springer J, Lackner M, Segura-Catena J, Canet LM, Alcazar-Fuoli L, López-Nevot MA, Fianchi L, Aguado JM, Pagano L, López-Fernández E, Alarcón-Riquelme M, Potenza L, Gonçalves SM, Luppi M, Moratalla L, Solano C, Sampedro A, González-Sierra P, Cuenca-Estrella M, Lagrou K, Maertens JA, Lass-Flörl C, Einsele H, Vazquez L; PCRAGA Study Group, Loeffler J, Ríos-Tamayo R, Carvalho A, Jurado M, Sainz J. Polymorphisms within the ARNT2 and CX3CR1 Genes Are Associated with the Risk of Developing Invasive Aspergillosis. Infect Immun. 2020 Mar 23;88(4):e00882-19. doi: 10.1128/IAI.00882-19. PMID: 31964743; PMCID: PMC7093133.
PUBMED DOIAre Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane).
Ceballos FC; Ryan P; Blancas R; et al; Jiménez-Sousa MÁ (20/20). Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality? Front Med (Laussane). 2021; 8:718053. PMID: 34660629. doi: 10.3389/fmed.2021.718053.
T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA; Jiménez JL; Bellón JM; et al (1/10). CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients: a retrospective study. J Acquir Immune Defic Syndr 2020 ;85(5):659-664. doi: 10.1097/QAI.0000000000002485.
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus.
Alcazar-Fuoli L, Clavaud C, Lamarre C, Aimanianda V, Seidl-Seiboth V, Mellado E, Latgé JP. Functional analysis of the fungal/plant class chitinase family in Aspergillus fumigatus. Fungal Genet Biol. 2011 Apr;48(4):418-29. doi: 10.1016/j.fgb.2010.12.007. Epub 2010 Dec 22. PMID: 21184840.
PUBMED DOIImpact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study.
Jiménez-Sousa MA (AC); Gómez-Moreno AZ; Pineda-Tenor D; et al. (1/9) Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9(4).
DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study.
Jiménez-Sousa MA (AC); Jiménez JL; Fernández-Rodríguez A; et al. (1/10). DBP rs16846876 and rs12512631 polymorphisms are associated with progression to AIDS naïve HIV-infected patients: a retrospective study. Journal of Biomedical Science. 2019; 23;26(1):83. doi: 10.1186/s12929-019-0577-y.
TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine.
Resino S; Fernández-Rodríguez A; Pineda-Tenor D; et al; Jiménez-Sousa MA. (11/11). 2021. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients.Journal of Clinical Medicine. 10-3, pp.483. ISSN 2077-0383. https://doi.org/10.3390/jcm10030483.
Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients
Salguero, Sergio; Rojo, David; Berenguer, Juan; et al; Jimenez-Sousa, Maria A. (AC) (15/15). 2020. Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients LIVER INTERNATIONAL. 40-9, pp.2215-2227. ISSN 1478-3223. https://doi.org/10.1111/liv.14580 3
Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals JOURNAL OF CLINICAL MEDICINE.
Molina-Carrion, Silvia; Brochado-Kith, Oscar; Gonzalez-Garcia, Juan; et al; Jimenez-Sousa, Maria Angeles. (12/12). 2020. Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals JOURNAL OF CLINICAL MEDICINE. 9. ISSN 2077-0383. https://doi.org/10.3390/jcm9082407.
PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients
Salguero, Sergio; Brochado-Kith, Oscar; Verdices, Ana Virseda; et al; Jiménez-Sousa María A (‡, AC); Resino, Salvador (‡, AC). (12/12). 2023. PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study. Biomedicine & pharmacotherapy. 159, pp.114220. ISSN 1950-6007.
Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology.
Virseda-Berdices, Ana; Concostrina-Martinez, Leyre; Martinez-Gonzalez, Oscar; et al; Fernandez-Rodriguez, Amanda (‡), Jiménez-Sousa María A (‡). (14/14). 2023. Relative telomere length impact on mortality of COVID-19: Sex differences.Journal of medical virology. 95-1, pp.e28368. ISSN 1096-9071.
Plasma miRNA profile at COVID-19 onset predicts severity status and mortality.
Fernandez-Pato, Asier; Virseda-Berdices, Ana; Resino, Salvador; et al; Jiménez-Sousa María A (‡, AC); Fernandez-Rodriguez, Amanda (‡). (20/20). 2022. Plasma miRNA profile at COVID-19 onset predicts severity status and mortality. EMERGING MICROBES & INFECTIONS. 11(1):676-688. doi: 10.1080/22221751.2022.2038021.
Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy.
Virseda-Berdices, Ana; Brochado-Kith, Oscar; Diez, Cristina; et al; Jimenez-Sousa, Maria Angeles. (16/16). 2021. Blood microbiome is associated with changes in portal hypertension after successful direct-acting antiviral therapy in patients with HCV-related cirrhosis.The Journal of antimicrobial chemotherapy. 77(3):719-726. doi: 10.1093/jac/dkab444. ISSN 1460-2091.
Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1
Barac A, Kosmidis C, Alastruey-Izquierdo A, Salzer HJF; CPAnet. Chronic pulmonary aspergillosis update: A year in review. Med Mycol. 2019 Apr 1;57(Supplement_2):S104-S109. doi: 10.1093/mmy/myy070. PMID: 30816975.
PUBMED DOILaursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun
Laursen CB, Davidsen JR, Van Acker L, Salzer HJF, Seidel D, Cornely OA, Hoenigl M, Alastruey-Izquierdo A, Hennequin C, Godet C, Barac A, Flick H, Munteanu O, Van Braeckel E. CPAnet Registry-An International Chronic Pulmonary Aspergillosis Registry. J Fungi (Basel). 2020 Jun 29;6(3):E96. doi: 10.3390/jof6030096. PMID: 32610566.
PUBMED DOITreatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018 Jul
Alastruey-Izquierdo A, Cadranel J, Flick H, Godet C, Hennequin C, Hoenigl M, Kosmidis C, Lange C, Munteanu O, Page I, Salzer HJF; on behalf of CPAnet. Treatment of Chronic Pulmonary Aspergillosis: Current Standards and Future Perspectives. Respiration. 2018 Jul 6:1-12. doi: 10.1159/000489474. [Epub ahead of print] Review. PMID: 29982245.
PUBMED DOIThe Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala. Open Forum Infect Dis. 2019 Dec
Samayoa B, Aguirre L, Bonilla O, Medina N, Lau-Bonilla D, Mercado D, Moller A, Perez JC, Alastruey-Izquierdo A, Arathoon E, Denning DW, Rodríguez-Tudela JL; “Fungired”. The Diagnostic Laboratory Hub: A New Health Care System Reveals the Incidence and Mortality of Tuberculosis, Histoplasmosis, and Cryptococcosis of PWH in Guatemala. Open Forum Infect Dis. 2019 Dec 15;7(1):ofz534. doi: 10.1093/ofid/ofz534. PMID: 31915715.
PUBMED DOIFungired. Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV. AIDS. 2020 Sep 1
Medina N, Alastruey-Izquierdo A, Mercado D, Bonilla O, Pérez JC, Aguirre L, Samayoa B, Arathoon E, Denning DW, Rodriguez-Tudela JL; Fungired. Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV. AIDS. 2020 Sep 1;34(11):1625-1632. doi: 10.1097/QAD.0000000000002631. PMID: 32694415.
PUBMED DOIPopulation-Based Program of filamentous fungi and Antifungal Resistance in Spain (FILPOP STUDY). Antimicrob Agents Chemother. 2013 Jul
Ana Alastruey-Izquierdo*, Emilia Mellado, Teresa Pelaez, Javier Pemán, Soledad Zapico, María Álvarez, Juan L Rodriguez-Tudela, Manuel Cuenca-Estrella Population-Based Program of filamentous fungi and Antifungal Resistance in Spain (FILPOP STUDY). Antimicrob Agents Chemother. 2013 Jul;57(7):3380-7. doi: 10.1128/AAC.01287-13. PMID: 28319466
PUBMED DOIThe global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 Dec
Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect Dis. 2017 Dec;17(12. doi: 10.1016/S1473-3099(17)30316-X. PMID: 28774698.
PUBMED DOIProject 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 Jun
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, Vicente Anza D, Viñuelas J, Zapico MS, Cuenca-Estrella M; members of 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 Jun 25. doi: 10.1128/AAC.00358-18. PMID: 29941643.
PUBMED DOIIn vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1
Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of APX001A against rare moulds using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 May 1;74(5):1295-1299. doi: 10.1093/jac/dkz022. PMID: 30753499.
PUBMED DOIIn vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 Jun 1
Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of olorofim (F901318) against clinical isolates of cryptic species of Aspergillus by EUCAST and CLSI methodologies. J Antimicrob Chemother. 2019 Jun 1;74(6):1586-1590. doi: 10.1093/jac/dkz078. PMID: 30891600.
PUBMED DOIMolecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain. Antimicrob Agents Chemother. 2019 Aug 23
Rivero-Menendez O, Soto-Debran JC, Medina N, Lucio J, Mellado E, Alastruey-Izquierdo A*. Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain. Antimicrob Agents Chemother. 2019 Aug 23;63(9). doi: 10.1128/AAC.00865-19. PMID: 31285229.
PUBMED DOIClinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization. Front Microbiol. 2019 Jul 11
Rivero-Menendez O, Navarro-Rodriguez P, Bernal-Martinez L, Martin-Cano G, Lopez-Perez L, Sanchez-Romero I, Perez-Ayala A, Capilla J, Zaragoza O, Alastruey-Izquierdo A*. Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization. Front Microbiol. 2019 Jul 11;10:1585. doi: 10.3389/fmicb.2019.01585. PMID: 31354675.
PUBMED DOIIn vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2020 Aug 28
Rivero-Menendez O, Cuenca-Estrella M, Alastruey-Izquierdo A.* In vitro activity of olorofim against clinical isolates of Scedosporium species and Lomentospora prolificans using EUCAST and CLSI methodologies. J Antimicrob Chemother. 2020 Aug 28. doi: 10.1093/jac/dkaa351. PMID:32856079.
PUBMED DOIEarly innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes.
Martín-Vicente M*, Resino S#, Martínez I#*. Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes. J Biomed Sci. 2022 Feb 13;29(1):11. doi: 10.1186/s12929-022-00793-3. PMID: 35152905 (R; FI= 12.771; D1 Medicine, Research & Experimental; JCR 2021).
PUBMEDHigh SARS-CoV-2 viral load and low CCL5 expression levels in the upper respiratory tract are associated with COVID-19 severity.
Pérez-García F, Martin-Vicente M, Rojas-García RL, Castilla-García L, Muñoz-Gomez MJ, Hervás Fernández I, González Ventosa V, Vidal-Alcántara EJ, Cuadros-González J, Bermejo-Martin JF, Resino S#, Martínez I#. High SARS-CoV-2 viral load and low CCL5 expression levels in the upper respiratory tract are associated with COVID-19 severity. J Infect Dis. 2022 Mar 15;225(6):977-982. doi: 10.1093/infdis/jiab604. PMID: 34910814 (A; FI= 7.759; Q1 Microbiology; JCR 2021).
PUBMEDNeighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study.
Álvaro-Meca A, Sepúlveda-Crespo D#, Resino R, Ryan P, Martínez I#, Resino S#. Neighborhood environmental factors linked to hospitalizations of older people for viral lower respiratory tract infections in Spain: a case-crossover study. Environ Health. 2022 Nov 8;21(1):107. doi: 10.1186/s12940-022-00928-x. PMID: 36348411.
PUBMEDDiagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.
Sepúlveda-Crespo D, Treviño-Nakoura A, Bellon JM, Jiménez-Sousa MA, Ryan P, Martínez I#, Fernández-Rodríguez A#, Resino S#. Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis. J Clin Microbiol. 2023 Jan 26; 61(1):e0133122. doi: 10.1128/jcm.01331-22. PMID: 36537787.
PUBMEDHCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients.
Brochado-Kith Ó, Martínez I*, Berenguer J, González-García J, Salgüero S, Sepúlveda-Crespo D, Díez C, Hontañón V, Ibañez-Samaniego L, Pérez-Latorre L, Fernández-Rodríguez A, Ángeles Jiménez-Sousa M, Resino S*. HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients. Front Immunol. 2021 Aug 23;12:723196. doi: 10.3389/fimmu.2021.723196. eCollection 2021.PMID: 34497613 (A; FI= 8.786; Q1 Immunology; JCR 2021).
PUBMEDHIV screening and retention in care in people who use drugs in Madrid, Spain: a prospective study
Ryan P, Valencia J, Cuevas G; Troya J; Torres-Macho J; Muñoz-Gómez MJ, Muñoz-Rivas N, Canorea I, Vázquez-Morón S (‡), Resino S (‡ *). HIV screening and retention in care in people who use drugs in Madrid, Spain: A prospective study. Infect Dis Poverty. 2021; 10(1): 111. (A; FI= 10.49; D1, Tropical Medicine; JCR 2021). PMID: 34412695. DOI: 10.1186/s40249-021-00894-5.
PUBMEDObesity-related SNPs and weight gain following first-line antiretroviral therapy.
Berenguer J (*), Jarrín I, Bellón JM, Díez C, Jiménez-Sousa MA, Roca C, González-García J, Dalmau D, Olalla J, Herrero C, Villarroya F, Domingo P, Resino S. Obesity-related SNPs and weight gain following first-line antiretroviral therapy. Clin Inf Dis. 2023; In press. (A; FI= 20.99; D1, Infectious Diseases; JCR 2021).
PUBMED DOIMild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study.
García-Broncano P, Medrano LM, Berenguer J, Brochado O, González-García J, Jiménez-Sousa MA, Quereda C, Sanz J, Téllez MJ, Díaz L, Jiménez JL, Muñoz-Fernández MA, Resino S (*). Mild profile improvement of immune biomarkers in HIV/HCV-coinfected patients who removed hepatitis C after HCV treatment: a prospective study. J Infect 2020; 80(1):99-110. (A; FI= 6.07; Q1, Infectious Diseases; JCR 2020). PMID: 31585189. DOI: 10.1016/j.jinf.2019.09.020.
PUBMEDEvaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia
Rueda C, Puig-Asensio M, Guinea J, Almirante B, Cuenca-Estrella M, Zaragoza O; CANDIPOP Project from GEIH-GEMICOMED (SEIMC) and REIPI. Evaluation of the possible influence of trailing and paradoxical effects on the clinical outcome of patients with candidemia. Clin Microbiol Infect. 2017 Jan;23(1):49.e1-49.e8.
PUBMED DOIIdentification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and Candida spp
Rossi SA, de Oliveira HC, Agreda-Mellon D, Lucio J, Mendes-Giannini MJS, García-Cambero JP, Zaragoza O. Identification of Off-Patent Drugs That Show Synergism with Amphotericin B or That Present Antifungal Action against Cryptococcus neoformans and Candida spp. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e01921-19. PMCID: PMC7179310.
PUBMED DOIParadoxical Growth of Candida albicans in the Presence of Caspofungin Is Associated with Multiple Cell Wall Rearrangements and Decreased Virulence
Rueda C, Cuenca-Estrella M, Zaragoza O. Paradoxical growth of Candida albicans in the presence of caspofungin is associated with multiple cell wall rearrangements and decreased virulence. Antimicrob Agents Chemother. 2014;58(2):1071-83. PMCID: PMC3910852.
PUBMED DOIHCV cure with direct-acting antivirals improves liver and immunological markers in HIV/HCV-coinfected patients.
Brochado-Kith O, Martínez I, Berenguer J, González-García J, Salgüero S, Sepúlveda-Crespo D, Díez C, Hontañón V, Ibañez-Samaniego L, Pérez-Latorre L, Fernández-Rodríguez A (‡), Jiménez-Sousa MA (‡), Resino S (‡ *). HCV cure with direct-acting antivirals improves liver and immunological markers in HIV/HCV-coinfected patients. Front immunol. 2021; 12:723196. (A; FI= 8.79; Q1, Immunology; JCR 2021). PMID: 34497613. DOI: 10.3389/fimmu.2021.723196.
PUBMEDCryptococcus neoformans induces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian model Galleria mellonella
Trevijano-Contador N, Herrero-Fernández I, García-Barbazán I, Scorzoni L, Rueda C, Rossi SA, García-Rodas R, Zaragoza O. Cryptococcus neoformans induces antimicrobial responses and behaves as a facultative intracellular pathogen in the non mammalian model Galleria mellonella. Virulence. 2015;6(1):66-74. PMCID: PMC4603429.
PUBMED DOIThe formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses
García-Barbazán I, Trevijano-Contador N, Rueda C, de Andrés B, Pérez-Tavárez R, Herrero-Fernández I, Gaspar ML, Zaragoza O. The formation of titan cells in Cryptococcus neoformans depends on the mouse strain and correlates with induction of Th2-type responses. Cell Microbiol. 2016 Jan;18(1):111-24.
PUBMED DOIContent with Investigacion .
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Adela González de la Campa
Scientific Investigator
ORCID code: 0000-0002-3598-2548
Dr. Adela González de la Campa obtained her degree in Biology in 1981 and her PhD in 1985 from the Complutense University of Madrid. She did her doctoral thesis in the laboratory of Dr. Miguel Vicente at the Centro de Investigaciones Biológicas of CSIC. Subsequently she worked for 2 years at Brookhaven National Laboratory, Upton, New York, USA in the laboratory of Sandford Lacks. After this postdoctoral stage in the USA, she worked for 3 years as a Reincorporation Fellow at the Centro de Investigaciones Biológicas of CSIC in the laboratory of Dr. Manuel Espinosa. He is a CSIC Senior Scientist since 1990 and Research Scientist since 2007. He participated as group leader of the CIBER of Respiratory Diseases (CIBERES) from 2007 to 2015. Since 1990, she has been the principal investigator of the Bacterial Genetics Unit at the National Centre for Microbiology.
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María José Ferrándiz Avellano
Research Scientist
ORCID code: 0000-0003-1428-9506
Dr. María José Ferrández obtained her degree in Biology in 1990 and her PhD in 1997 from the Complutense University of Madrid. She completed her doctoral thesis at the Centro de Investigaciones Biológicas of CSIC in the laboratory of Dr. Miguel Vicente. She completed her postdoctoral training at the Centro Nacional de Microbiología of Instituto de Salud Carlos III (1998-2001 and 2003-2006) and at the Institute of Infection and Immunity (University of Nottingham) from 2001- 2003. From 2007 to 2015, she participated as a researcher of the CIBER of Respiratory Diseases (CIBERES). Since 2006, she is a Full Scientist at the National Microbiology Center of the ISCIII.
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Mónica Amblar Esteban
Research Scientist
ORCID code: 0000-0003-3530-615X
Dr. Mónica Amblar obtained her degree in Biology in 1993 and her PhD in 2000 from the Complutense University of Madrid. She did her doctoral thesis in the laboratory of Dr. Paloma López at the Centro de Investigaciones Biológicas of CSIC. Subsequently, she worked for 5 and half years at the Instituto de Tecnología Química e Biológica/Universidade Nova de Lisboa, Oeiras (Portugal) in the laboratory of Prof. Cecilia M. Arraiano. After this postdoctoral stage he rejoined the Centro de Investigaciones Biológicas del CSIC where he worked for 2 years as a Postdoctoral Researcher in the laboratory of Dr. Paloma López. Subsequently, he joined the National Microbiology Center of the ISCIII with a Ramón y Cajal contract and in 2010 he obtained a position as a Full Scientist at the same center.
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Noelia Martínez Montes
FP2 Technician
Technician in Clinical and Biomedical Laboratory from IES Moratalaz in 2019. Worked for 10 months as a Technician in the Emergency Laboratory at Reina Sofía University Hospital and for 1 year and 9 months in various laboratories at La Paz University Hospital. Since March 2023, has been working in our laboratory at the National Center for Microbiology of ISCIII under a Laboratory Technician contract within the Youth Guarantee Plan of the Community of Madrid.
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Laura Alfonso Alarcón
PhD student
ORCID code: 0000-0003-1560-1100
Degree in Biochemistry in 2020 from National University of Asunción (Paraguay). Master in Microbiology and Health in 2024 from Pais Vasco University (Spain). Stays in Paraguay in Instituto de Investigaciones en Ciencias de la Salud; Facultad de Ciencias Químicas and Hospital Nacional de Itaugua. She is actually a predoctoral student of the Microbiología y Parasitología program of Complutense University of Madrid, with a “Don Carlos Antonio López” (BECAL) fellowship from Paraguay Goverment.
List of staff
Información adicional
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.