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Bacterial Genetics
Research Lines
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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
Multidisciplinary Group of viral coinfection HIV/Hepatitis (COVIHEP). HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study.
López-Huertas MR, Palladino C, Garrido-Arquero M, Esteban-Cartelle B, Sánchez-Carrillo M, Martínez-Román P, Martín-Carbonero L, Ryan P, Domínguez-Domínguez L, Santos ID, Moral SDLF, Benito JM, Rallón N, Alcamí J, Resino S, Fernández-Rodríguez A, Coiras M, Briz V*, on behalf of the Multidisciplinary Group of viral coinfection HIV/Hepatitis (COVIHEP). HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: a cross-sectional study. Sci Rep 2019: 9 (1); 5606.
PUBMED DOIPersistent Low-Level Viremia in treatment HIV infection: An unresolved status.
3. Crespo-Bermejo C, Ramírez de Arellano E, Lara-Aguilar V, Martínez-Román P, Arca Lafuente S, Gómez-Lus ML, Martín-Carbonero L, Briz V. Persistent Low-Level Viremia in treatment HIV infection: An unresolved status. Virulencia 2021, 12: 2919-2931.
PUBMED DOIFull coding hepatitis E virus genotype 3 genome amplification method.
Muñoz-Chimeno M, Forero JE, Echevarría JM, Muñoz-Bellido JL, Vázquez-López L, Morago L, García-Galera MC, Avellón A. Full coding hepatitis E virus genotype 3 genome amplification method. J Virol Methods. 2016 Apr;230:18-23.
PUBMED DOIComparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection.
• Avellón A, Morago L, García-Galera del Carmen M, Muñoz M, Jose-Manuel Echevarría JM. Comparative sensitivity of commercial tests for hepatitis E genotype 3 virus antibody detection. J Med Virol. 2015 Nov;87(11):1934-9.
PUBMED DOIEpidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain
11: Puig-Asensio M, Padilla B, Garnacho-Montero J, Zaragoza O, Aguado JM, Zaragoza R, Montejo M, Muñoz P, Ruiz-Camps I, Cuenca-Estrella M, Almirante B; CANDIPOP Project; GEIH-GEMICOMED (SEIMC); REIPI. Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect. 2014 Apr;20(4):O245-54.
PUBMED DOIB Pérez de Val, B Romero, MT Tórtola, L Herrera-León, P Pozo, I Mercader, JL Sáez, M Domingo, E Vidal. Poly-resistant Mycobacterium bovis infection in a human and sympatric sheep, Spain, 2017-2018
B Pérez de Val, B Romero, MT Tórtola, L Herrera-León, P Pozo, I Mercader, JL Sáez, M Domingo, E Vidal. Poly-resistant Mycobacterium bovis infection in a human and sympatric sheep, Spain, 2017-2018. Emerg Infect Dis. 2021 Apr;27(4):1241-1243. doi: 10.3201/eid2704.204467. PMID: 33755008.
DOIL Bernal-Martínez; L Herrera-Leon; C Valero; P de la Cruz; L Ghimpu; AC Mesa-Arango; G Santoni; L Goterris; R Millán; MJ Buitrago. Differential Diagnosis of Fungal Pneumonias vs.Tuberculosis in AIDS Patients by Using Two New Molecular Methods.
L Bernal-Martínez; L Herrera-Leon; C Valero; P de la Cruz; L Ghimpu; AC Mesa-Arango; G Santoni; L Goterris; R Millán; MJ Buitrago. Differential Diagnosis of Fungal Pneumonias vs.Tuberculosis in AIDS Patients by Using Two New Molecular Methods. J. Fungi 2021, 7, 336. doi.org: 10.3390/jof7050336. PMID: 33925404.
DOIE Tagliani, RAnthony, TA Kohl, A de Neeling, V Nikolayevskyy, C Ködmön, FP Maurer, S Niemann, D van Soolingen, MJ van der Werf, D Cirillo, ECDC molecular surveillance project participants. Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017-2019: an ECDC pilot study
E Tagliani, RAnthony, TA Kohl, A de Neeling, V Nikolayevskyy, C Ködmön, FP Maurer, S Niemann, D van Soolingen, MJ van der Werf, D Cirillo, ECDC molecular surveillance project participants. Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017-2019: an ECDC pilot study. Eur Respir J. 2021 Jan 5;57(1):2002272. doi: 10.1183/13993003.02272-2020. Print 2021 Jan. PMID: 32732329.
DOIMJ Iglesias, D Ibarz, A Cebollada, J Comín, MS Jiménez, MC Vázquez, S Samper, Spanish Working Group on MDRTB. The value of the continuous genotyping of multidrug resistant tuberculosis over 20 years in Spain.
MJ Iglesias, D Ibarz, A Cebollada, J Comín, MS Jiménez, MC Vázquez, S Samper, Spanish Working Group on MDRTB. The value of the continuous genotyping of multidrug resistant tuberculosis over 20 years in Spain. Sci Rep. 2020 Nov 24;10(1):20433. doi: 10.1038/s41598-020-77249-x. PMID: 33235225.
DOIS Campos-Gutierrez, MJ Ramos-Real, R Abreu, MS Jimenez, M Lecuona. Pseudo-ourbreak of Mycobacterium fortuitum, in a hospital bronchoscopy unit.
S Campos-Gutierrez, MJ Ramos-Real, R Abreu, MS Jimenez, M Lecuona. Pseudo-ourbreak of Mycobacterium fortuitum, in a hospital bronchoscopy unit. Am J Infect Control. 2020 Jul;48(7):765-769. doi: 10.1016/j.ajic.2019.11.019. Epub 2019 Dec 24. PMID: 31882175.
DOIGascha , Y Meijeb, M Espasac, B Fonta, MS Jiménez, N Fernández-Hidalgo. Disseminated Infection Due to Mycobacterium chimaera After Aortic Valve Replacement.
Gascha , Y Meijeb, M Espasac, B Fonta, MS Jiménez, N Fernández-Hidalgo. Disseminated Infection Due to Mycobacterium chimaera After Aortic Valve Replacement. Revista Española de cardiología. 2019. Vol 72 (6):502-503. DOI: 10.1016/j.rec.2018.06.026. PMID: 30029979
DOIPBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study
2. Salgüero S, Brochado-Kith O, Virseda Verdices A, Berenguer J, González-García J, Martínez I, Díez C, Hontañón V, Pérez-Latorre L, Fernández-Rodríguez A (‡), Jiménez-Sousa MA (‡,*), and Resino S (‡, *). PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study. Biomed Pharmacother 2023, 159:114220. (A; FI= 7.42; D1, Pharmacology & Pharmacy; JCR 2021). PMID: 36628818. DOI: 10.1016/j.biopha.2023.114220.
PUBMEDLow anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients
4. Martin-Vicente M, Almansa R, Martínez I, Tedim AP, Bustamante E, Tamayo L, Aldecoa C, Gómez JM, Renedo G, Berezo JA, Cedeño JA, Mamolar N, García Olivares P, Herrán-Monge R, Cicuendez R, Enríquez P, Ortega A, Jorge N, Doncel C, 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, Domínguez-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, 291(2):232–240. (A; FI= 13.07; D1, Medicine, General & Internal; JCR 2021). PMID: 34611927. DOI: 10.1111/joim.13386.
PUBMEDPrevalence 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.
PUBMEDEnvironmental 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.
PUBMEDDetection 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.
PUBMEDMaría 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
DOIJordi 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.
DOIHCV 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.
PUBMEDRelationship 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.
PUBMEDContent with Investigacion .
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Horacio Gil Gil
Research Scientist
ORCID code: 0000-0002-7114-6686
Degree in Veterinary Medicine in 1995 and PhD in Veterinary Medicine in 2002 from the University of Zaragoza. He did his PhD thesis at NEIKER Tecknalia (Derio, Vizcaya) and the National Center for Microbiology of Instituto de Salud Carlos III (CNM-ISCIII, Majadahonda, Madrid) on the biological cycle of Lyme disease in the Basque Country. After that, he developed his postdoctoral training in different aspects of the pathogenesis of tularemia at the Center for Infectious Diseases, Stony Brook University, New York (USA) for 3 years. In December 2005, he joined the Reference and Research Laboratory in Special Pathogens of the CNM-ISCIII where he developed diagnostic, reference and research activities, in Bartonella, Leptospira and pathogens of interest in bioterrorism. Between 2014-2016 he participated in the European Program for the Training of Microbiologists in Public Health (EUPHEM), organized by the European Centre for Disease Prevention and Control. During this program, he participated in an international mission for the investigation of a cholera outbreak in Ghana, proposed by the Bernhard Nocht Institute for Tropical Diseases in Hamburg (Germany). In December 2016, he worked as a laboratory consultant for the World Health Organization at their office in Phnom Penh (Cambodia). Subsequently, he worked one year with Médecins Sans Frontières as director and quality manager of the TB laboratory in Nukus (Uzbekistan).
In 2019, he joined the HIV Variability and Biology Unit at CNM-ISCIII, where he developed different reference and research activities, including his contribution to the molecular epidemiological surveillance of HIV-1 in Spain and the study of HIV-1 antiretroviral resistance. Since September 2022 he has been leading the Human Papillomavirus Unit at the CNM-ISCIII. -
Alicia Inés García Señán
Predoctoral Student UNED
Degree in Pharmacy in 2013 from the Complutense University of Madrid. She completed specialized health training in Microbiology and Parasitology at the Complejo Asistencial Universitario de Salamanca (2014-2018). During this period he studied a master's degree in Tropical Diseases at the University of Salamanca (2016). She has developed her professional activity as a clinical microbiologist at the Hospital de Santa Bárbara (Soria) (2018), Hospital Universitario Vall d'Hebrón (Barcelona) (2019-2022), and Hospital Central de la Defensa (Gómez Ulla) C.S.V.E, since 2022. In September 2024 she has started PhD studies at the Human Papillomavirus Unit of the CNM-ISCIII.
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Manuela Rodríguez Vargas
Técnico de Laboratorio
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.