Bacterial Genetics
Research Lines
Content with Investigacion .
The Laboratory of Medical Entomology (LME) develops an intense reference and research activity, focused on the field of disease vectors of interest in Public Health. The LME has an insectary where biological cycles of insect vectors are currently maintained, allowing the performance, among others, of vector competence and xenodiagnostic studies. The LME supports the national health system by offering techniques available in the portfolio of services for the taxonomic identification of arthropods of health interest. In addition, it performs entomological surveillance of outbreaks, supporting Surveillance Plans. In particular, the LME plays a leading role in the Entomological Surveillance Plan for Leishmaniasis in the Community of Madrid. On the other hand, the LME offers scientific advice to the CCAES (Centro de Coordinación de Alertas y Emergencias Sanitarias, Ministerio de Sanidad, Consumo y Bienestar Social), and participates in the elaboration of reports and rapid risk assessments.
The main research lines of the Laboratory of Medical Entomology are:
1. Maintenance of insect vector colonies: phlebotomine sand flies (Phlebotomus perniciosus, Phlebotomus papatasi and Phlebotomus argentipes, vectors of Leishmania infantum, Leishmania major and Leishmania donovani, respectively), Culex and Aedes mosquitoes (vectors of various arboviruses) and Rhodnius prolixus (vector of Trypanosoma cruzi).
2. Biology of disease vectors of public health interest: biology, vector competence, experimental infections. The CNM has a BSL3 safety laboratory to carry out vector competence studies with culicidae and phlebotomine sand flies.
3. Entomological sampling, infectivity of potential reservoirs of leishmaniasis.
4. Insecticides and repellents: evaluation of their efficacy.
5. Characterization of saliva proteins of hematophagous Diptera: genomics, proteomics, biochemistry and gene editing. Study of salivary proteins as markers of bite exposure, virulence factors and/or vaccines.
6. Xenodiagnosis of leishmaniasis.
7. Molecular biology and taxonomy of phlebotomine sand flies. Molecular detection of Leishmania infantum in phlebotomine sand flies and characterization of Leishmania spp. Molecular identification of blood ingested by vectors.
Research projects
Content with Investigacion .
CURRENT PROJECTS
Project title: "Biochemical and functional characterisation of salivary proteins of Phlebotomus perniciosus and their role in infection by Leishmania infantum (PERNIPROT)"Reference: Project PID2023-147773NA-I00 funded by MICIU/AEI/10.13039/501100011033 and by FEDER, EU.
Start date: 01/09/2024
End date: 31/08/2028
Funding: €175,000
Principal investigator: Inés Elena Martín Martín.
Funding agency: Agencia Estatal de Investigación (Proyecto de Generación del Conocimiento 2023).
Project title: "Surveillance of leishmaniasis in the Community of Madrid from a “One Health” perspective: study of the infectious capacity of patients with visceral leishmaniasis and their role as reservoirs"
Reference: PI24CIII/00026
Start date: 01/01/2025
End date: 31/12/2027
Funding: €60,000.00
Principal investigator: Inés Elena Martín Martín.
Co-principal investigator: Maribel Jiménez Alonso
Funding agency: Instituto de Salud Carlos III (Strategic Action in Intramural Health, AESI).
Service Contract: "Analysis for the surveillance of the vector and wild reservoirs that transmit leishmaniasis in the Community of Madrid"
Reference: file no. 17/2024 (A/SER-008455/2024).
Start date: 26/06/2024
End date: 10/12/25, extendable to 2026
Total funding: €171,084
Principal Investigator: Maribel Jiménez Alonso
Funding agency: Service Contract between the Instituto de Salud Carlos III and the Directorate-General for Public Health, Regional Ministry of Health of the Community of Madrid
Project Title: CIBERINFEC Research Group (CB21/13/00110)
Start date: 2021
End date: currently active
Principal Investigator: Dr. Mª Paz Sánchez-Seco, Arbovirus and Imported Viral Diseases Unit.
Researchers from the Medical Entomology Laboratory: Maribel Jiménez (member), Inés Martín Martín (collaborator).
Funding: €108,134. File number: CB21/13/00110.
Funding agency: Consortium Centre for Biomedical Research in NETWORK (CIBER)
PAST PROJECTS
Service Contract: "Evaluation of the anti-leishmania effect of the bacteria Tc1 and its derivatives in the intravectorial cycle"
Reference: ISCIII-06896
Start date: 15/12/2022
End date: 15/04/2025
Funding: €71,265.67
Principal Investigator: Inés Elena Martín Martín
Funding agency: Service Contract between the company GlaxoSmithKline R&D (GSK) and the Instituto de Salud Carlos III
Service Contract: "Analysis for the surveillance of the vector and wild reservoirs that transmit leishmaniasis in the Community of Madrid"
Reference: 59/2020 (A/SER-040739/2020)
Start date: 10/12/2021
End date: 10/12/2023.
Funding: €42,612.17 per year Total 2021-2023: €127,836.51
Principal Investigators: Ricardo Molina /Maribel Jiménez Alonso
Funding agency: Service contract between the Instituto de Salud Carlos III (ISCIII) and the Directorate-General for Public Health, Regional Ministry of Health of the Community of Madrid
Project title: "Research and Integrated Surveillance of Emerging Arboviruses West Nile, Toscana and Dengue in some areas of Spain"
Reference: PI19CIII/00014
Start date: 2020
End date: 2022
Principal Investigator: Ana Vázquez González
Co-Principal Investigator: Ricardo Molina
Funding: €60,000.00
Funding agency: Instituto de Salud Carlos III (Strategic Action in Intramural Health, AESI).
Project title: "Characterisation of the concept of ‘asymptomatic carrier’ in leishmaniasis: implications for treatment".
Start date: 01/01/2015
End date: 31/12/2017
Principal investigators: Javier Moreno and Javier García
Funding: €159,940
Funding agency: Study Agreement between Drugs for Neglected Diseases Initiative (DNDi), the Spanish Foundation for International Cooperation, Health and Social Policy (FCSAI) and Fuenlabrada Hospital. Subcontractor: ISCIII Medical Entomology Unit (Maribel Jiménez and Ricardo Molina).
Project title: "Biology and control of vector-borne infections in Europe (EDENext Collaborative Project): Sandfly-borne diseases".
Reference: Subproject (PBD) (EU, FP7-HEALTH-2010-single-stage, contract No. 261504).
Start date: 2011
End date: 2014
Principal investigator: Ricardo Molina General coordinator: Petr Volf
Funding: €140,000
Funding agency: EU-FP7
Project Title: "Phlebotomus perniciosus saliva as a source in the search for potential targets for the development of vaccines against Leishmania infantum"
Reference: AGL2008-01592/GAN (MICINN)
Start date: 2009
End date: 2011
Principal investigator: Ricardo Molina
Funding: €70,180
Funding agency: Ministry of Science and Innovation
Publications
Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19. García-Ríos, E.; Leivas, A.; Mancebo, F.J.; Sánchez-Vega, L.; Lanzarot, D.; Aguado, J.M.; Martínez-López, J.; Paciello, M.L.; Pérez-Romero, P. Biomedicines 2022, 10, 630. doi: 10.3390/biomedicines10030630.
Isolation of Functional SARS-CoV-2 Antigen-Specific T-Cells with Specific Viral Cytotoxic Activity for Adoptive Therapy of COVID-19. García-Ríos, E.; Leivas, A.; Mancebo, F.J.; Sánchez-Vega, L.; Lanzarot, D.; Aguado, J.M.; Martínez-López, J.; Paciello, M.L.; Pérez-Romero, P. Biomedicines 2022, 10, 630. doi: 10.3390/biomedicines10030630.
Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome. Mancebo, F.J., Parras-Moltó, M., García-Ríos, E., Pérez-Romero, P. International Journal of Molecular Sciences, 2022, 23(5), 2768. doi: 10.3390/ijms23052768.
Deciphering the Potential Coding of Human Cytomegalovirus: New Predicted Transmembrane Proteome. Mancebo, F.J., Parras-Moltó, M., García-Ríos, E., Pérez-Romero, P. International Journal of Molecular Sciences, 2022, 23(5), 2768. doi: 10.3390/ijms23052768.
Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance
Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins. Tajuelo, A.; López-Siles, M.; Más, V.; Pérez-Romero, P.; Aguado, J.M.; Briz, V.; McConnell, M.J.; Martín-Galiano, A.J.; López, D. Int. J. Mol. Sci. 2022, 23, 2977. doi: 10.3390/ijms23062977.
PUBMEDDetection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance
Immunogenicity of Anti-SARS-CoV-2 Vaccines in Common Variable Immunodeficiency. Arroyo-Sánchez D, Cabrera-Marante O, Laguna-Goya R, Almendro-Vázquez P, Carretero O, Gil-Etayo FJ, Suàrez-Fernández P, Pérez-Romero, P, Rodríguez de Frías E, Serrano A, Allende LM, Pleguezuelo D, Paz-Artal E. J Clin Immunol. 2022 Feb;42(2):240-252. doi: 10.1007/s10875-021-01174-5. PMID: 34787773.
PUBMEDOptimization of a Lambda-RED Recombination Method for Rapid Gene Deletion in Human Cytomegalovirus
Optimization of a Lambda-RED Recombination Method for Rapid Gene Deletion in Human Cytomegalovirus. García-Ríos E, Gata-de-Benito J, López-Siles M, McConnell MJ, Pérez-Romero, P. Int J Mol Sci. 2021 Sep 29;22(19):10558. doi: 10.3390/ijms221910558. PMID: 34638896.
PUBMEDCirculatory follicular helper T lymphocytes associate with lower incidence of CMV infection in kidney transplant recipients
Circulatory follicular helper T lymphocytes associate with lower incidence of CMV infection in kidney transplant recipients. Suàrez-Fernández P, Utrero-Rico A, Sandonis V, García-Ríos E, Arroyo-Sánchez D, Fernández-Ruiz M, Andrés A, Polanco N, González-Cuadrado C, Almendro-Vázquez P, Pérez-Romero P, Aguado JM, Paz-Artal E, Laguna-Goya R. Am J Transplant. 2021 Dec;21(12):3946-3957. doi: 10.1111/ajt.16725. PMID: 34153157.
PUBMEDIs It Feasible to Use CMV-Specific T-Cell Adoptive Transfer as Treatment Against Infection in SOT Recipients?
Is It Feasible to Use CMV-Specific T-Cell Adoptive Transfer as Treatment Against Infection in SOT Recipients? García-Ríos E, Nuévalos M, Mancebo FJ, Pérez-Romero P. Front Immunol. 2021 Apr 23;12:657144. doi: 10.3389/fimmu.2021.657144. PMID: 33968058.
PUBMEDCytotoxic cell populations developed during treatment with tyrosine kinase inhibitors protect autologous CD4+ T cells from HIV-1 infection
Cytotoxic cell populations developed during treatment with tyrosine kinase inhibitors protect autologous CD4+ T cells from HIV-1 infection. Vigón L, Rodríguez-Mora S, Luna A, Sandonís V, Mateos E, Bautista G, Steegmann JL, Climent N, Plana M, Pérez-Romero P, de Ory F, Alcamí J, García-Gutierrez V, Planelles V, López-Huertas MR, Coiras M. Biochem Pharmacol. 2020 Aug 20;182:114203. doi: 10.1016/j.bcp.2020.114203. PMID: 32828803
PUBMEDRole of Neutralizing Antibodies in CMV Infection: Implications for New Therapeutic Approaches
Role of Neutralizing Antibodies in CMV Infection: Implications for New Therapeutic Approaches. Sandonís V, García-Ríos E, McConnell MJ, Pérez-Romero P.Sandonís V, et al. Trends Microbiol. 2020 Nov;28(11):900-912. doi: 10.1016/j.tim.2020.04.003. PMID: 32448762 Review.
PUBMEDPre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients
Pre-existing Hemagglutinin Stalk Antibodies Correlate with Protection of Lower Respiratory Symptoms in Flu-Infected Transplant Patients. Aydillo T, Escalera A, Strohmeier S, Aslam S, Sanchez-Cespedes J, Ayllon J, Roca-Oporto C, Pérez-Romero P, Montejo M, Gavalda J, Munoz P, Lopez-Medrano F, Carratala J, Krammer F, García-Sastre A, Cordero E. Cell Rep Med. 2020 Nov 3;1(8):100130. doi: 10.1016/j.xcrm.2020.100130. PMID: 33294855
PUBMEDEffect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients. Cordero E, Bulnes-Ramos A, Aguilar-Guisado M, González Escribano F, Olivas I, Torre-Cisneros J, Gavaldá J, Aydillo T, Moreno A, Montejo M, Fariñas MC, Carratalá J, Muñoz P, Blanes M, Fortún J, Suárez-Benjumea A, López-Medrano F, Roca C, Lara R, Pérez-Romero P. Front Immunol. 2020 Oct 6;11:1917. doi: 10.3389/fimmu.2020.01917. PMID: 33123119
Effect of Influenza Vaccination Inducing Antibody Mediated Rejection in Solid Organ Transplant Recipients. Cordero E, Bulnes-Ramos A, Aguilar-Guisado M, González Escribano F, Olivas I, Torre-Cisneros J, Gavaldá J, Aydillo T, Moreno A, Montejo M, Fariñas MC, Carratalá J, Muñoz P, Blanes M, Fortún J, Suárez-Benjumea A, López-Medrano F, Roca C, Lara R, Pérez-Romero P. Front Immunol. 2020 Oct 6;11:1917. doi: 10.3389/fimmu.2020.01917. PMID: 33123119
Humoral response to natural influenza infection in solid organ transplant recipients
Humoral response to natural influenza infection in solid organ transplant recipients. Hirzel C, Ferreira VH, L'Huillier AG, Hoschler K, Cordero E, Limaye AP, Englund JA, Reid G, Humar A, Kumar D; Influenza in Transplant Study Group.Hirzel C, et al. Am J Transplant. 2019 Aug;19(8):2318-2328. doi: 10.1111/ajt.15296. Epub 2019 Mar 18.Am J Transplant. 2019. PMID: 30748090 Clinical Trial.
PUBMEDA 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients
A 5-Year Prospective Multicenter Evaluation of Influenza Infection in Transplant Recipients. Kumar D, Ferreira VH, Blumberg E, Silveira F, Cordero E, Perez-Romero P, Aydillo T, Danziger-Isakov L, Limaye AP, Carratala J, Munoz P, Montejo M, Lopez-Medrano F, Farinas MC, Gavalda J, Moreno A, Levi M, Fortun J, Torre-Cisneros J, Englund JA, Natori Y, Husain S, Reid G, Sharma TS, Humar A.Kumar D, et al. Clin Infect Dis. 2018 Oct 15;67(9):1322-1329. doi: 10.1093/cid/ciy294.Clin Infect Dis. 2018. PMID: 29635437 Clinical Trial.
PUBMEDImpact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study
Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study. Molina-Ortega A, Martín-Gandul C, Mena-Romo JD, Rodríguez-Hernández MJ, Suñer M, Bernal C, Sánchez M, Sánchez-Céspedes J, Pérez Romero P, Cordero E.Molina-Ortega A, et al. Clin Microbiol Infect. 2019 Jun;25(6):753-758. doi: 10.1016/j.cmi.2018.09.019. PMID: 30292792 Clinical Trial.
PUBMEDTwo Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1-2, a Randomized Controlled Clinical Trial.
Two Doses of Inactivated Influenza Vaccine Improve Immune Response in Solid Organ Transplant Recipients: Results of TRANSGRIPE 1-2, a Randomized Controlled Clinical Trial. Cordero E, Roca-Oporto C, Bulnes-Ramos A, Aydillo T, Gavaldà J, Moreno A, Torre-Cisneros J, Montejo JM, Fortun J, Muñoz P, Sabé N, Fariñas MC, Blanes-Julia M, López-Medrano F, Suárez-Benjumea A, Martinez-Atienza J, Rosso-Fernández C, Pérez-Romero P. Clin Infect Dis. 2017 Apr 1;64(7):829-838. doi: 10.1093/cid/ciw855.Clin Infect Dis. 2017. PMID: 28362949 Clinical Trial.
PUBMEDUse of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation
Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation. Blanco-Lobo P, Cordero E, Martín-Gandul C, Gentil MA, Suárez-Artacho G, Sobrino M, Aznar J, Pérez-Romero P.Blanco-Lobo P, et al. J Infect. 2016 May;72(5):597-607. doi: 10.1016/j.jinf.2016.02.008. Epub 2016 Feb 24.J Infect. 2016. PMID: 26920791 Clinical Trial.
PUBMEDIdentification and Analysis of Unstructured, Linear B-Cell Epitopes in SARS-CoV-2 Virion Proteins for Vaccine Development
Identification and Analysis of Unstructured, Linear B-Cell Epitopes in SARS-CoV-2 Virion Proteins for Vaccine Development. Corral-Lugo A, López-Siles M, López D, McConnell MJ, Martin-Galiano AJ. Vaccines. 2020 Jul 20;8(3):397. doi: 10.3390/vaccines8030397.
PUBMEDUsing Omics Technologies and Systems Biology to Identify Epitope Targets for the Development of Monoclonal Antibodies Against Antibiotic-Resistant Bacteria
Using Omics Technologies and Systems Biology to Identify Epitope Targets for the Development of Monoclonal Antibodies Against Antibiotic-Resistant Bacteria. Martín-Galiano AJ, McConnell MJ.Front Immunol. 2019 Dec 10;10:2841. doi: 10.3389/fimmu.2019.02841. eCollection 2019.
PUBMEDA lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection
A lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection. Pulido MR, García-Quintanilla M, Pachón J, McConnell MJ.Vaccine. 2020 Jan 22;38(4):719-724. doi: 10.1016/j.vaccine.2019.11.043.
PUBMEDA Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa.
A Live Salmonella Vaccine Delivering PcrV through the Type III Secretion System Protects against Pseudomonas aeruginosa. Aguilera-Herce J, García-Quintanilla M, Romero-Flores R, McConnell MJ, Ramos-Morales F. mSphere. 2019 Apr 17;4(2):e00116-19. doi: 10.1128/mSphere.00116-19.
PUBMEDContent with Investigacion .
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Maribel Jiménez Alonso
Tenured Scientist
ORCID code: 0000-0002-5615-3087
Doctor in Pharmacy from the Complutense University of Madrid (1994) and Extraordinary Doctorate Award. She started her research activity at ISCIII in 1990 in the field of leishmaniasis. Currently, she is the head of the LEM where she develops her scientific work in the field of entomological surveillance of phlebotomine sandflies in the CM and other studies in the field of molecular biology, mainly applied to the model of Leishmania infantum and its vector Phlebotomus perniciosus. Member of the team of experts of the ISCIII that participates in the elaboration of Rapid Risk Assessments and in the working groups in charge of the elaboration of National Plans of Prevention, Surveillance and Control of Vector-borne Diseases of the CCAES, Ministry of Health. She is currently “Operational Focal Point” for vector-borne diseases at national level for the One Health-Vectornet network (EFSA and ECDC) and coordinator of the VectorNet-Spain network since July 2024. In addition, she is a member of the expert committee of the Network of Surveillance and Control of Vectors with public health interest in the Community of Madrid. In addition, she is part of a research group from CIBER (CIBERINFEC; CB21/13/00110).
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Inés Martín Martín
Tenured Scientist
ORCID code: 0000-0002-0956-7324
Within Medical Entomology, my work focuses on the study of phlebotomine sand flies and culicidae as vectors of leishmaniasis and arbovirosis, respectively. In 2014 I obtained my PhD degree “cum laude” with European mention from the Complutense University of Madrid. My PhD Thesis (developed at the Instituto de Salud Carlos III), focused on the study of phlebotomine sandfly saliva. Subsequently, during my postdoctoral period, I worked on insect gene editing, molecular, biochemical and functional characterization of insect saliva proteins and their role in the infection and transmission of pathogens. Most of my scientific career has been developed at the Laboratory of Malaria and Vector Research, National Institutes of Health (NIH), USA. Since 2021 I am a Senior Scientist at the Laboratory of Medical Entomology (ISCIII).
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Ricardo Molina Moreno
Doctor Ad Honorem
ORCID code: 0000-0001-6662-173X
Doctor in Biological Sciences from the Complutense University of Madrid (1994). In 1979 he began his professional career at the Instituto de Salud Carlos III (ISCIII), where he became a researcher in 1985. He was in charge of the Medical Entomology Laboratory from that year until his retirement in 2023. He is currently a doctor linked “Ad Honorem”. He has extensive experience in medical entomology, advising the Ministry of Health (CCAES) and Health Departments of Autonomous Communities, on surveillance and control of arthropods transmitting vector-borne diseases. In recent years he has been involved in surveillance programs in Spain for leishmaniasis vectors, especially in the Fuenlabrada outbreak, and for viruses causing Crimean-Congo hemorrhagic fever and dengue. Also in the surveillance of invasive exotic mosquitoes, especially Aedes albopictus, in ports and airports. In his last stage he has been part of the research group within the CIBER (CIBERINFEC; CB21/13/00110).
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Marcos López de Felipe Escudero
Predoctoral contract FPU
ORCID code: 0000-0002-2919-836X
Graduated in Biology from the Autonomous University of Madrid and Master in Tropical Parasitic Diseases from the University of Valencia. He started his professional career in 2019 in surveillance and management of hematophagous diptera of veterinary-medical interest, as well as other urban pests. In 2024 he began his work at the Instituto de Salud Carlos III (ISCIII) within the framework of the project “Evaluation of the anti-leishmanicidal effect of the bacterium Tc1 and its derivatives in the intravectorial cycle of the parasite” directed by Dr. Inés Martín Martín where he continues after the award of a FPU fellowship. He has extensive experience in medical entomology, especially in surveillance and vector control and taxonomic identification. Her career so far has focused mainly on the study of phlebotomine sand flies, simulids and culicidae, with special attention to citizen science.
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Eva Pérez Martínez
Clinical and Biomedical Laboratory Technician
ORCID code: 0000-0002-6553-9969
Graduated in 2019 from the Advanced Vocational Training Program in Clinical and Biomedical Laboratory Sciences. I began my professional career in 2020 at Eurofins Megalab laboratories. In 2024, I started working as a freelance professional on an international project focused on the bioecology of phlebotomine sand flies in urban environments across the Mediterranean Basin, conducting fieldwork in Spain, Italy, Greece, and southern France within the framework of citizen science. Since 2025, I have been part of the Medical Entomology Laboratory at the Instituto de Salud Carlos III (ISCIII), where I work as a laboratory technician on the project “Biochemical and functional characterization of salivary proteins from Phlebotomus perniciosus and their role in Leishmania infantum infection (PERNIPROT)”, led by Dr. Inés Martín Martín.
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.