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Viral Biology

Research Lines

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.

Research projects

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.
 

Publications

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European collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants

• Avellón A, Echevarría JM, Weber B, Weik M, Schobel U, Willems WR, Gerlich WH. European collaborative evaluation of the Enzygnost HBsAg 6.0 assay: performance on hepatitis B virus surface antigen variants. J Med Virol. 2011 Jan;83(1):95-100.

PUBMED DOI

Prevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain.

Prevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain. Nguyen LTT*, Román F*, Morikawa K, Trincado P, Marcos C, Rojo-Martín MD, Cafini F. Int J Antimicrob Agents. 2018 Aug;52(2):305-306.

PUBMED DOI

Zoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics

Rodriguez-Pastor, Ruth; Escudero, Raquel; Lambin, Xavier; Vidal, M Dolors; Gil, Horacio; Jado, Isabel; Rodriguez-Vargas, Manuela; Luque-Larena, Juan Jose; Mougeot, Francois. Zoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics. Parasitology. pp. 1 - 10. 24/09/2018.

PUBMED DOI

Long-range dispersal moved Francisella tularensis into Western Europe from the East

Dwibedi, Chinmay; Birdsell, Dawn; Larkeryd, Adrian; Myrtennas, Kerstin; Ohrman, Caroline; Nilsson, Elin; Karlsson, Edvin; Hochhalter, Christian; Rivera, Andrew; Maltinsky, Sara; Bayer, Brittany; Keim, Paul; Scholz, Holger C; Tomaso, Herbert; Wittwer, Matthias; Beuret, Christian; Schuerch, Nadia; Pilo, Paola; Hernandez Perez, Marta; Rodriguez-Lazaro, David; Escudero, Raquel; Anda, Pedro; Forsman, Mats; Wagner, David M; Larsson, Par; Johansson, Anders. Long-range dispersal moved Francisella tularensis into Western Europe from the East. Microbial genomics. 2 - 12, pp. e000100. 01/01/2016.

PUBMED DOI

Francisella species in ticks and animals, Iberian Peninsula

Lopes de Carvalho, I.; Toledo, A.; Carvalho, C. L.; Barandika, J. F.; Respicio-Kingry, L. B.; Garcia-Amil, C.; Garcia-Perez, A. L.; Olmeda, A. S.; Ze-Ze, L.; Petersen, J. M.; Anda, P.; Nuncio, M. S.; Escudero, R. Francisella species in ticks and animals, Iberian Peninsula. Ticks and Tick-Borne Diseases. 7 - 1, pp. 159 - 165. Elsevier GMBH, Urban & Fischer Verlag, 01/01/2016.

PUBMED DOI

Stable levels of Coxiella burnetii prevalence in dairy sheep flocks but changes in genotype distribution after a 10-year period in northern Spain

Álvarez-Alonso R, Barandika JF, Ruiz-Fons F, Ortega-Araiztegi I, Jado I, Hurtado A, García-Pérez AL. Stable levels of Coxiella burnetii prevalence in dairy sheep flocks but changes in genotype distribution after a 10-year period in northern Spain. Acta Vet Scand. 2018 Nov 20;60(1):75.

PUBMED DOI

First case of a naturally acquired human infection with Plasmodium cynomolgi

Ta TH, Hisam S, Lanza M, Jiram AI, Ismail N, Rubio JM. (2014). First case of a naturally acquired human infection with Plasmodium cynomolgi. Malar J. 2014 Feb 24;13(1):68.

PUBMED DOI

Evidence for Suppression of Onchocerciasis Transmission in Bioko Island, Equatorial Guinea

Moya L, Herrador Z, Ta-Tang TH, Rubio JM, Perteguer MJ, Hernandez-González A, García B, Nguema R, Nguema J, Ncog P, Garate T, Benito A, Sima A and Aparicio P. Evidence for Suppression of Onchocerciasis Transmission in Bioko Island, Equatorial Guinea.PLoS Negl Trop Dis, 2016; 10(7): e0004829.

PUBMED DOI

Content with Investigacion Genética Bacteriana .

List of staff

Additional Information

The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.

Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).

Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.

Safe and effective vaccines against these viruses are currently not available.  Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.

On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.

The research activity of the Viral Biology group since its beginnings in the 1980s has focused on respiratory viruses, especially on the study of the mechanisms of virus entry into the cell, evolutionary aspects, antigenic properties and vaccine development.

Currently, the group's objectives are focused on the characterisation of the immune response and the development of vaccines against human pneumoviruses: human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV).

Both viruses are considered to be important respiratory pathogens of high clinical relevance, especially in the paediatric population.

Safe and effective vaccines against these viruses are currently not available.  Soluble protein subunits based on the fusion protein (F-protein) of hRSV and hMPV are being developed in the laboratory by protein engineering for use as vaccines against human pneumoviruses.

On the other hand, and thanks to the characterisation of the type of humoral response induced by the F proteins of these viruses, the laboratory is also involved in the isolation of monoclonal antibodies and nanoantibodies for use as treatments against these viruses.

Content with Investigacion Genética Bacteriana .