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Bacterial Genetics

Líneas de investigación

Content with Investigacion Genética Bacteriana .

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 Genética Bacteriana .

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.
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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

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Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort

5. Berenguer J (*), Díez C, Martín-Vicente M, Mican R, Pérez-Elías MJ, García-Fraile LJ, Vidal F, Suárez-García I, Podzamcer D, Del Romero J, Pulido F, Iribarren JA, Gutiérrez F, Poveda E, Galera C, Izquierdo R, Asensi V, Portilla J, López JC, Arribas JR, Moreno S, González-García J, Resino S (‡), Jarrín I (‡). Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort. Clin Microbiol Infect. 2021, 27(11):1678-1684. (A; FI= 13.31; D1, Microbiology; JCR 2021). PMID: 34186209 DOI: 10.1016/j.cmi.2021.06.023.

PUBMED

Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study

6. Álvaro-Meca A, Goez MC, Resino R, Matías V, Sepúlveda-Crespo D; Martínez I, Resino S (*). Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: a bidirectional case-crossover study. Environ Res. 2022. 212(Pt B), 113319. (A; FI= 8.43; D1, Public, Environmental & Occupational Health; JCR 2021). PMID: 35447151. DOI: 10.1016/j.envres.2022.113319.

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Detection of active hepatitis C in a single visit and linkage to care among marginalized people using a mobile unit in Madrid, Spain

7. Ryan P, Valencia J, Cuevas G, Torres-Macho J, Troya J, Pueyo A, Muñoz-Gómez MJ, Muñoz-Rivas N, Vázquez-Morón S, Martínez, I, Lazarus JV, Resino S (*). Detection of active hepatitis C in a single visit and link-to-care among excluded people using a mobile unit in Madrid, Spain. Int J Drug Policy. 2021, 96:103424. (A; FI= 5.93; Q1, Substance Abuse; JCR 2021). PMID: 34429222 DOI: 10.1016/j.drugpo.2021.103424.

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María José Ruiz-Lopéz, Milagros Muñoz-Chimeno, Jordi Figuerola, Ana M. Gavilán, Sarai Varona, Isabel Cuesta, Josué Martínez-de la Puente, Angel Zaballos, Francisca Molero, Ramón C. Soriguer, Mª Paz Sánchez-Seco, Santiago Ruiz, Ana Vázquez. Genomic analysis of West Nile virus lineage 1 isolated from mosquitoes

María José Ruiz-Lopéz, Milagros Muñoz-Chimeno, Jordi Figuerola, Ana M. Gavilán, Sarai Varona, Isabel Cuesta, Josué Martínez-de la Puente, Angel Zaballos, Francisca Molero, Ramón C. Soriguer, Mª Paz Sánchez-Seco, Santiago Ruiz, Ana Vázquez. Genomic analysis of West Nile virus lineage 1 isolated from mosquitoes from 2020-2021 outbreak occurred in Andalusia, Spain. Viruses 2023, 15, 266. https://doi.org/10.3390/v15020266

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Jordi Figuerola, Miguel Ángel Jiménez-Clavero, María José Ruíz-López, Francisco Llorente, Santiago Ruiz, Andreas Hoefer, Pilar Aguilera-Sepúlveda, Jéssica Jiménez Peñuela1, Olaya García-Ruiz, Laura Herrero, Ramón C. Soriguer, Raúl Fernández Delgado, Mari Paz Sánchez-Seco, Josué Martínez-de la Puente, Ana Vázquez. A One Health view of the West Nile virus outbreak in Andalusía (Spain) in 2020

Jordi Figuerola, Miguel Ángel Jiménez-Clavero, María José Ruíz-López, Francisco Llorente, Santiago Ruiz, Andreas Hoefer, Pilar Aguilera-Sepúlveda, Jéssica Jiménez Peñuela1, Olaya García-Ruiz, Laura Herrero, Ramón C. Soriguer, Raúl Fernández Delgado, Mari Paz Sánchez-Seco, Josué Martínez-de la Puente, Ana Vázquez. A One Health view of the West Nile virus outbreak in Andalusía (Spain) in 2020. Emerg Microbes Infect. 2022 Dec;11(1):2570-2578. doi: 10.1080/22221751.2022.2134055.

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HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients.

10.1186/s40249-021-00894-5. 9. Brochado O, Martínez I (*), Berenguer J, Medrano L, González-García J, Jiménez-Sousa MA, Carrero A, Hontañón V, Navarro J, Guardiola JM, Pérez-Latorre L, Micán R, Fernández-Rodríguez A (‡), Resino S (* ‡). HCV eradication with IFN-based therapy does not completely restore gene expression in PBMCs from HIV/HCV-coinfected patients. J Biomed Sci 2021; 28:23 (A; FI= 12.77; D1, Medicine, Research & Experimental; JCR 2021). PMID: 33785040. DOI: 10.1186/s12929-021-00718-6.

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Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis.

12. García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa Ma, Fernández-Rodríguez A, Guzmán-Fulgencio M; Resino S (*). Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis. Hepatology. 2014, 6(5):1541-1550. (A; FI= 11.05; D1, Gastroenterology & Hepatology; JCR 2014). PMID: 24975775. DOI: 10.1002/hep.27281.

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FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients.

13. Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, García-Álvarez M, Aldamiz-Echevarría T, Carrero A, Vázquez-Morón S, García-Broncano P, Diez C, Tejerina F, Guzmán-Fulgencio M, Resino S (*). FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients. BMC Med. 2014, 12:198. (A; FI= 7.34; D1, Medicine, General & Internal; JCR 2014). PMID: 25367448. DOI: 10.1186/s12916-014-0198-y.

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HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy.

14. Guzmán-Fulgencio M, Berenguer J; Rallón N, Fernández-Rodríguez A, Miralles P, Soriano V, Jiménez-Sousa MA, Cosin J, Medrano J, García-Álvarez M, López JC, Benito JM, Resino S (*). HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy. AIDS 2013; 27(8):1231-1238. (A; FI= 6.55; D1, Infectious Diseases; JCR 2013). PMID: 23811951. DOI: 10.1097/QAD.0b013e32835f5b9c.

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Eva Orviz, Anabel Negredo, Oskar Ayerdi, Ana Vázquez, Ana Muñoz-Gomez, Sara Monzón, Petunia Clavo, Angel Zaballos, Mar Vera, Patricia Sánchez, Noemi Cabello, Pilar Jiménez, Jorge A Pérez-García, Sarai Varona, Jorge Del Romero, Isabel Cuesta, Alberto Delgado-Iribarren, Montse Torres, Iñigo Sagastagoitia, Gustavo Palacios, Vicente Estrada, Maria Paz Sánchez-Seco, Grupo Viruela del Simio Madrid CNM/ISCIII/HCSC/Sandoval.

Eva Orviz, Anabel Negredo, Oskar Ayerdi, Ana Vázquez, Ana Muñoz-Gomez, Sara Monzón, Petunia Clavo, Angel Zaballos, Mar Vera, Patricia Sánchez, Noemi Cabello, Pilar Jiménez, Jorge A Pérez-García, Sarai Varona, Jorge Del Romero, Isabel Cuesta, Alberto Delgado-Iribarren, Montse Torres, Iñigo Sagastagoitia, Gustavo Palacios, Vicente Estrada, Maria Paz Sánchez-Seco, Grupo Viruela del Simio Madrid CNM/ISCIII/HCSC/Sandoval. Monkeypox outbreak in Madrid (Spain): Clinical and virological aspects. J Infect. 2022 Jul 10;S0163-4453(22)00415-7. doi: 10.1016/j.jinf.2022.07.005.

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European mitochondrial haplogroups are associated with CD4+ T-cell recovery in HIV-infected patients on combination antiretroviral therapy.

15. ​Guzmán-Fulgencio M; Berenguer J, Micheloud D, Fernández-Rodríguez A; García–Álvarez M, Jiménez-Sousa MA, Bellón JM, Campos Y, Cosin J, Aldámiz-Echevarría T, Catalán P, López JC, Resino S (*). European mitochondrial haplogroups are associated with CD4+ T-cell recovery in HIV-infected patients on combination antiretroviral therapy. J Antimicrob Chemoth 2013; 68 (10): 2349–2357 (A; FI= 5.44; D1, Infectious Diseases; JCR 2013). PMID: 23749950. DOI: 10.1093/jac/dkt206.

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María Paz Sánchez-Seco, María José Sierra, Agustín Estrada-Peña, Félix Valcárcel, Ricardo Molina, Eva Ramírez de Arellano, Angeles Sonia Olmeda, Lucía García San Miguel, Maribel Jiménez, Luis J Romero, Anabel Negredo; Group for CCHFv Research. Widespread Detection of Multiple Strains of Crimean-Congo Hemorrhagic Fever Virus in Ticks, Spain.

María Paz Sánchez-Seco, María José Sierra, Agustín Estrada-Peña, Félix Valcárcel, Ricardo Molina, Eva Ramírez de Arellano, Angeles Sonia Olmeda, Lucía García San Miguel, Maribel Jiménez, Luis J Romero, Anabel Negredo; Group for CCHFv Research. Widespread Detection of Multiple Strains of Crimean-Congo Hemorrhagic Fever Virus in Ticks, Spain. Emerg Infect Dis. 2022 Feb;28(2):394-402. doi: 10.3201/eid2802.211308.

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Negredo A, Sánchez-Ledesma M, Llorente F, Pérez-Olmeda M, Belhassen-García M, González-Calle D, Sánchez-Seco MP, Jiménez-Clavero MÁ. Retrospective Identification of Early Autochthonous Case of Crimean-Congo Hemorrhagic Fever, Spain, 2013

Negredo A, Sánchez-Ledesma M, Llorente F, Pérez-Olmeda M, Belhassen-García M, González-Calle D, Sánchez-Seco MP, Jiménez-Clavero MÁ. Retrospective Identification of Early Autochthonous Case of Crimean-Congo Hemorrhagic Fever, Spain, 2013. Emerg Infect Dis. 2021 Jun;27(6):1754-1756. doi: 10.3201/eid2706.204643.

DOI

Negredo A, Sánchez-Arroyo R, Díez-Fuertes F, de Ory F, Budiño MA, Vázquez A, Garcinuño Á, Hernández L, la Hoz González C, Gutiérrez-Arroyo A, Grande C, Sánchez-Seco P. Fatal Case of Crimean-Congo Hemorrhagic Fever Caused by Reassortant Virus, Spain, 2018.

Negredo A, Sánchez-Arroyo R, Díez-Fuertes F, de Ory F, Budiño MA, Vázquez A, Garcinuño Á, Hernández L, la Hoz González C, Gutiérrez-Arroyo A, Grande C, Sánchez-Seco P. Fatal Case of Crimean-Congo Hemorrhagic Fever Caused by Reassortant Virus, Spain, 2018. Emerg Infect Dis. 2021 Apr;27(4):1211-1215. doi: 10.3201/eid2704.203462.

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Laura Davó, Laura Herrero, Maria Paz Sánchez-Seco, Nuria Labiod, David Roiz, Elena Gómez-Díaz, Lourdes Hernandez, Jordi Figuerola and Ana Vázquez. Real-time PCR assay to detect Granada virus and the related Massilia and Arrabida phleboviruses

Laura Davó, Laura Herrero, Maria Paz Sánchez-Seco, Nuria Labiod, David Roiz, Elena Gómez-Díaz, Lourdes Hernandez, Jordi Figuerola and Ana Vázquez. Real-time PCR assay to detect Granada virus and the related Massilia and Arrabida phleboviruses. Davó et al. Parasit Vectors. 2020 May 29;13(1):270. doi: 10.1186/s13071-020-04110-5.

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María Velasco, María Paz Sánchez-Seco, Carolina Campelo, Fernando de Ory, Oriol Martin, Laura Herrero, Octavio J. Salmerón Béliz, Teodora Minguito, Mª Carmen Campos, Francisca Molero, Alejandro Algora and Ana Vázquez. Imported Human West Nile Virus Lineage 2 Infection in Spain

María Velasco, María Paz Sánchez-Seco, Carolina Campelo, Fernando de Ory, Oriol Martin, Laura Herrero, Octavio J. Salmerón Béliz, Teodora Minguito, Mª Carmen Campos, Francisca Molero, Alejandro Algora and Ana Vázquez. Imported Human West Nile Virus Lineage 2 Infection in Spain: Neurological and Gastrointestinal Complications. Viruses 2020 Jan 29;12(2):156. doi: 10.3390/v12020156.

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Negredo A, Habela MÁ, Ramírez de Arellano E, Diez F, Lasala F, López P, Sarriá A, Labiod N, Calero-Bernal R, Arenas M, Tenorio A, Estrada-Peña A, Sánchez-Seco MP. Survey of Crimean-Congo Hemorrhagic Fever Enzootic Focus, Spain, 2011-2015

Negredo A, Habela MÁ, Ramírez de Arellano E, Diez F, Lasala F, López P, Sarriá A, Labiod N, Calero-Bernal R, Arenas M, Tenorio A, Estrada-Peña A, Sánchez-Seco MP. Survey of Crimean-Congo Hemorrhagic Fever Enzootic Focus, Spain, 2011-2015. Emerg Infect Dis. 2019 Jun;25(6):1177-1184. doi: 10.3201/eid2506.180877.

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Ramírez de Arellano E, Sanchez-Lockhart M, Perteguer MJ, Bartlett M, Ortiz M, Campioli P, Hernández A, Gonzalez J, Garcia K, Ramos M, Jiménez-Clavero MÁ, Tenorio A, Sánchez-Seco MP, González F, Echevarría JE, Palacios G, Negredo A. First Evidence of Antibodies Against Lloviu Virus in Schreiber's Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain

Ramírez de Arellano E, Sanchez-Lockhart M, Perteguer MJ, Bartlett M, Ortiz M, Campioli P, Hernández A, Gonzalez J, Garcia K, Ramos M, Jiménez-Clavero MÁ, Tenorio A, Sánchez-Seco MP, González F, Echevarría JE, Palacios G, Negredo A. First Evidence of Antibodies Against Lloviu Virus in Schreiber's Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain. Viruses. 2019 Apr 19;11(4):360. doi: 10.3390/v11040360.

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Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals.

3. Sepúlveda-Crespo D, Treviño-Nakoura A, Bellon JM, Ardizone Jiménez B, Jiménez‑Sousa MA, Fernández-Rodríguez A, Martínez I (‡), Resino S (*‡). Meta-analysis: diagnostic accuracy of hepatitis C core antigen detection during therapy with direct-acting antivirals. Aliment Pharmacol Ther 2022; 56 (8): 1224-1234 (A; FI= 9.52; D1, Pharmacology & Pharmacy; JCR 2021).

PUBMED DOI

Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later.

4. Martin-Vicente M, Carrasco I, Muñoz-Gomez MJ, Lobo AH, Mas V, Vigil-Vázquez S, Vázquez M, Manzanares A, Cano O, Alonso R, Sepúlveda-Crespo D, Tarancón-Díez L, Muñoz-Fernández MÁ, Muñoz-Chapuli M, Resino S#*, Navarro ML#, Martinez I#*. Antibody levels to SARS-CoV-2 spike protein in mothers and children from delivery to six months later. Birth. 2022 Jul 8:10.1111/birt.12667. doi: 10.1111/birt.12667. Online ahead of print. PMID: 35802776.

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Hepatitis E virus seroprevalence is associated with neurodegenerative disorders in older people with dementia: a case-control study.

5. Pérez-García F, Vázquez-Morón S, Burgueño-García I, José Muñoz-Gómez M, Zea-Sevilla MA, Calero M, Martínez I#, Rábano A#, Resino S#. Hepatitis E virus seroprevalence is associated with neurodegenerative disorders in older people with dementia: a case-control study. J Infect Dis. 2022 Jun 27:jiac268. doi: 10.1093/infdis/jiac268. Online ahead of print. PMID: 35759220 (A; FI= 7.759; Q1 Microbiology; JCR 2021).

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Negative impact of HIV infection on broad-spectrum anti-HCV neutralizing antibody titers in HCV-infected patients with advanced HCV-related cirrhosis.

6. Sepúlveda-Crespo D, Yélamos MB, Díez C, Gómez J, Hontañón V, Torresano-Felipe F, Berenguer J, González-García J, Ibañez-Samaniego L, Llop E, Olveira A, Martínez J, Resino S (‡ *), Martínez I (‡ *). Negative impact of HIV infection on broad-spectrum anti-HCV neutralizing antibody titers in HCV-infected patients with advanced HCV-related cirrhosis. Biomed Pharmacother 2022, 150: 113024. (A; FI= 7.42; D1, Pharmacology & Pharmacy; JCR 2021).

PUBMED DOI

. Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study.

7. Álvaro-Meca A, Goez MDC, Resino R, Matías V, Sepúlveda-Crespo D, Martínez I#, Resino S#. Environmental factors linked to hospital admissions in young children due to acute viral lower respiratory infections: A bidirectional case-crossover study. Environ Res. 2022 Sep; 212(Pt B):113319. doi: 10.1016/j.envres.2022.113319. PMID: 35447151. (A; FI= 8.431; D1 Public, Environmental & Occupational Health; JCR 2021).

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Misdiagnosis rate of among negative COVID-19 patients in real-life with Panbio COVID-19 Antigen Rapid Test during 2021.

8. Ryan P, Pérez-García F, Torres-Macho J, Bibiano C, Ignacio Lazo J, Castaño-Ochoa G, Vidal-Alcántara EJ, Muñoz-Gómez MJ, Martínez I#, Resino S#. Misdiagnosis rate of among negative COVID-19 patients in real-life with Panbio COVID-19 Antigen Rapid Test during 2021. J Infect. 2022 May; 84(5):e42-e44. doi: 10.1016/j.jinf.2022.03.013. PMID: 35306106 (L; FI= 38.637; D1 Infectious Diseases; JCR 2021).

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Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19.

11. Martín-Vicente M, Berenguer J, Muñoz-Gómez MJ, Díez C, Micán R, Pérez-Elías MJ, García-Fraile LJ, Peraire J, Suárez-García I, Jiménez-Sousa MÁ, Fernández-Rodríguez A, Vázquez M, Ryan P, González-García J, Jarrín I, Mas V, Martínez I#, Resino S#. Similar humoral immune responses against the SARS-CoV-2 spike protein in HIV and non-HIV individuals after COVID-19. J Infect. 2022 Mar;84(3):418-467. doi: 10.1016/j.jinf.2021.11.002. PMID: 34752819 (L; FI= 38.637; D1 Infectious Diseases; JCR 2021).

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Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

12. Martin-Vicente M#, Almansa R#, Martínez I#, Tedim AP, Bustamante E, Tamayo L, Aldecoa C, Gómez JM, Renedo G, Berezo JÁ, Cedeño JA, Mamolar N, García Olivares P, Herrán-Monge R, Cicuendez R, Enríquez P, Ortega A, Jorge N, Doncel C, de la Fuente A, Bustamante-Munguira J, Muñoz-Gómez MJ, González-Rivera M, Puertas C, Más V, Vázquez M, Pérez-García F, Rico-Feijoo J, Martín S, Motos A, Fernandez-Barat L, Eiros JM, Dominguez-Gil M, Ferrer R, Barbé F, Trapiello W, Kelvin DJ, Bermejo-Martin JF, Resino S, Torres A. Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients. J Intern Med. 2022 Feb; 291(2):232-240. doi: 10.1111/joim.13386. PMID: 34611927 (A; FI= 13.068; D1 Medicine, General & Internal; JCR 2021).

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Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis.

13. Sepulveda-Crespo D, Resino S*, Martinez I*. Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis. Drugs. 2021 Drugs. 2021 Mar; 81(4):419-443. doi: 10.1007/s40265-020-01458-x. PMID: 33400242. (R; FI= 11.431; D1 Pharmacology & Pharmacy; JCR 2021).

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Contribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression. Valenzuela-Fernández A, Cabrera-Rodríguez R, Casado C, Pérez-Yanes S, Pernas M, García-Luis J, Marfil S, Olivares I, Estévez-Herrera J, Trujillo-González R, Blanco J, Lopez-Galindez C

Contribution of the HIV-1 Envelope Glycoprotein to AIDS Pathogenesis and Clinical Progression. Valenzuela-Fernández A, Cabrera-Rodríguez R, Casado C, Pérez-Yanes S, Pernas M, García-Luis J, Marfil S, Olivares I, Estévez-Herrera J, Trujillo-González R, Blanco J, Lopez-Galindez C. Biomedicines. 2022 Sep 2,10(9):2172. doi: 10.3390/biomedicines10092172.

DOI

The Characteristics of the HIV-1 Env Glycoprotein Are Linked with Viral Pathogenesis. Pérez-Yanes S, Pernas M, Marfil S, Cabrera-Rodríguez R, Ortiz R, Urrea V, Rovirosa C, Estévez-Herrera J, Olivares I, Casado C, Lopez-Galindez C, Blanco J, Valenzuela-Fernández A

The Characteristics of the HIV-1 Env Glycoprotein Are Linked with Viral Pathogenesis. Pérez-Yanes S, Pernas M, Marfil S, Cabrera-Rodríguez R, Ortiz R, Urrea V, Rovirosa C, Estévez-Herrera J, Olivares I, Casado C, Lopez-Galindez C, Blanco J, Valenzuela-Fernández A. Front Microbiol. 2022 Mar 24, 3:763039. doi: 10.3389/fmicb.2022.763039. eCollection 2022.

DOI

Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Moyano A, Blanch-Lombarte O, Tarancon-Diez L, Pedreño-Lopez N, Arenas M, Alvaro T, Casado C, Olivares I, Vera M, Rodriguez C, Del Romero J, López-Galíndez C, Ruiz-Mateos E, Prado JG, Pernas M.

Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control. Moyano A, Blanch-Lombarte O, Tarancon-Diez L, Pedreño-Lopez N, Arenas M, Alvaro T, Casado C, Olivares I, Vera M, Rodriguez C, Del Romero J, López-Galíndez C, Ruiz-Mateos E, Prado JG, Pernas M. Retrovirology. 2022 Mar 26,19(1):6. doi: 10.1186/s12977-022-00591-7.

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Viral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors. Colomer-Lluch M, Kilpelainen A, Pernas M, Peña R, Ouchi D, Jimenez-Moyano E, Dalmau J, Casado C, López-Galíndez C, Clotet B, Martinez-Picado J, Prado JG

Viral and Cellular Factors Leading to the Loss of CD4 Homeostasis in HIV-1 Viremic Nonprogressors. Colomer-Lluch M, Kilpelainen A, Pernas M, Peña R, Ouchi D, Jimenez-Moyano E, Dalmau J, Casado C, López-Galíndez C, Clotet B, Martinez-Picado J, Prado JG. J Virol. 2022 Jan 12, 96(1): e0149921. doi: 10.1128/JVI.01499-21. Epub 2021 Oct 20.

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Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses. Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V, Yuste E. J Virol.

Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses. Beltran-Pavez C, Bontjer I, Gonzalez N, Pernas M, Merino-Mansilla A, Olvera A, Miro JM, Brander C, Alcami J, Sanders RW, Sanchez-Merino V, Yuste E. J Virol. 2022 Jan 12, 96(1): e0134321. doi: 10.1128/JVI.01343-21. Epub 2021 Oct 20.

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High-Risk Sexual Practices Contribute to HIV-1 Double Infection Among Men Who Have Sex with Men in Madrid. Casado C, Pernas M, Rava M, Ayerdi O, Vera M, Alenda R, Jiménez P, Docando F, Olivares I, Zaballos A, Vicario JL, Rodríguez C, Del Romero J, Lopez-Galindez C.

High-Risk Sexual Practices Contribute to HIV-1 Double Infection Among Men Who Have Sex with Men in Madrid. Casado C, Pernas M, Rava M, Ayerdi O, Vera M, Alenda R, Jiménez P, Docando F, Olivares I, Zaballos A, Vicario JL, Rodríguez C, Del Romero J, Lopez-Galindez C. AIDS Res Hum Retroviruses. 2020 Nov, 36(11):896-904. doi: 10.1089/AID.2020.0068. Epub 2020 Aug 19.

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Unintended HIV-1 Infection During Analytical Therapy Interruption.Ugarte A, Romero Y, Tricas A, Casado C, Lopez-Galindez C, Garcia F, Leal L.

Unintended HIV-1 Infection During Analytical Therapy Interruption.Ugarte A, Romero Y, Tricas A, Casado C, Lopez-Galindez C, Garcia F, Leal L. J Infect Dis. 2020 Apr 27,221(10):1740-1742. doi: 10.1093/infdis/jiz611

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Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure. Casado C, Galvez C, Pernas M, Tarancon-Diez L, Rodriguez C, Sanchez-Merino V, Vera M, Olivares I, De Pablo-Bernal R, Merino-Mansilla A, Del Romero J, Lorenzo-Redondo R, Ruiz-Mateos E, Salgado M, Martinez-Picado J, Lopez-Galindez C

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure. Casado C, Galvez C, Pernas M, Tarancon-Diez L, Rodriguez C, Sanchez-Merino V, Vera M, Olivares I, De Pablo-Bernal R, Merino-Mansilla A, Del Romero J, Lorenzo-Redondo R, Ruiz-Mateos E, Salgado M, Martinez-Picado J, Lopez-Galindez C. Sci Rep. 2020 Feb 5,10(1):1902. doi: 10.1038/s41598-020-58696-y.

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Characterizing the antiviral effect of an ATR inhibitor on human immunodeficiency virus type 1 replication. Docando F, Casado C, Pernas M, Mota-Biosca A, López-Galíndez C, Olivares I

Characterizing the antiviral effect of an ATR inhibitor on human immunodeficiency virus type 1 replication. Docando F, Casado C, Pernas M, Mota-Biosca A, López-Galíndez C, Olivares I. Arch Virol. 2020 Mar, 165(3):683-690. doi: 10.1007/s00705-020-04531-8. Epub 2020 Jan 30.

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Elite controllers and lessons learned for HIV-1 cure. Lopez-Galindez C, Pernas M, Casado C, Olivares I, Lorenzo-Redondo R

Elite controllers and lessons learned for HIV-1 cure. Lopez-Galindez C, Pernas M, Casado C, Olivares I, Lorenzo-Redondo R. Curr Opin Virol. 2019 Oct, 38:31-36. doi: 10.1016/j.coviro.2019.05.010. Epub 2019 Jun 27.

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HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic. Cabrera-Rodríguez R, Hebmann V, Marfil S, Pernas M, Marrero-Hernández S, Cabrera C, Urrea V, Casado C, Olivares I, Márquez-Arce D, Pérez-Yanes S, Estévez-Herrera J, Clotet B, Espert L, López-Galíndez C, Biard-Piechaczyk M, Valenzuela-Fernández A, Blanco J.

HIV-1 envelope glycoproteins isolated from Viremic Non-Progressor individuals are fully functional and cytopathic. Cabrera-Rodríguez R, Hebmann V, Marfil S, Pernas M, Marrero-Hernández S, Cabrera C, Urrea V, Casado C, Olivares I, Márquez-Arce D, Pérez-Yanes S, Estévez-Herrera J, Clotet B, Espert L, López-Galíndez C, Biard-Piechaczyk M, Valenzuela-Fernández A, Blanco J. Sci Rep. 2019 Apr 3,9(1):5544. doi: 10.1038/s41598-019-42075-3.

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Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers. Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera MS, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C.

Viral Characteristics Associated with the Clinical Nonprogressor Phenotype Are Inherited by Viruses from a Cluster of HIV-1 Elite Controllers. Casado C, Marrero-Hernández S, Márquez-Arce D, Pernas M, Marfil S, Borràs-Grañana F, Olivares I, Cabrera-Rodríguez R, Valera MS, de Armas-Rillo L, Lemey P, Blanco J, Valenzuela-Fernández A, Lopez-Galíndez C. mBio. 2018 Apr 10,9(2): e02338-17. doi: 10.1128/mBio.02338-17.

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Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. Pernas M, Tarancón-Diez L, Rodríguez-Gallego E, Gómez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, León A, Rodriguez C, Benito JM, Rallón N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, García F, Alcamí J, Muñoz-Fernández M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. J Virol

Factors Leading to the Loss of Natural Elite Control of HIV-1 Infection. Pernas M, Tarancón-Diez L, Rodríguez-Gallego E, Gómez J, Prado JG, Casado C, Dominguez-Molina B, Olivares I, Coiras M, León A, Rodriguez C, Benito JM, Rallón N, Plana M, Martinez-Madrid O, Dapena M, Iribarren JA, Del Romero J, García F, Alcamí J, Muñoz-Fernández M, Vidal F, Leal M, Lopez-Galindez C, Ruiz-Mateos E. J Virol. 2018 Feb 12,92(5): e01805-17. doi: 10.1128/JVI.01805-17.

DOI

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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 Genética Bacteriana .