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results is carried out using different mice models or in zebrafish embryos. In addition, we also study other compounds with antibacterial activity, such as bicyclic amine esters that behave like choline analogues, an amino alcohol essential for pneumococcal survival.
Another aspect of marked interest for our group, consists in the identification of S. pneumoniae proteins
as possible virulence factors, analyzing the molecular mechanisms involved in evasion of the host immune response using human cell lines and murine models of infection. Moreover, our research team participates in the characterization of new pneumococcal proteins to be used as novel antigens in the development of protein vaccines in the future.
Most relevant scientific articles
• Diez-Martinez R., Garcia-Fernandez E., Manzano M., Martinez A., Domenech M., Vallet-Regi M. et al. Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections. Scientific Reports. 2016;6.
• Ramos-Sevillano E., Urzainqui A., de Andres B., Gonzalez-Tajuelo R., Domenech M., Gonzalez-Camacho F. et al. PSGL-1 on Leukocytes is a Critical Component of the Host Immune Response against Invasive Pneumococcal Disease. PLoS Pathogens. 2016;12(3).
• Blazquez B., Fresco-Taboada A., Iglesias-Bexiga M., Menendez M., Garcia P.. PL3 amidase, a tailor-made lysin constructed by domain shuffling with potent killing activity against pneumococci and related species. Frontiers in Microbiology. 2016;7(JUL).
• Domenech M., Pedrero-Vega E., Prieto A., Garcia E. Evidence of the presence of nucleic acids and β-glucan in the matrix of non-typeable Haemophilus influenzae in vitro biofilms. Scientific Reports. 2016;6.
• Corsini B., Aguinagalde L., Ruiz S., Domenech M., Antequera M.L., Fenoll A. et al. Immunization with LytB protein of Streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis. Vaccine. 2016;34(50):6148-6157.
Highlights
• The P-selectin glycoprotein ligand-1 (PSGL-1) on leukocytes is involved in the phagocytosis process of S. pneumoniae by targeting the capsule and the surface protein LytA playing a critical protective role against invasive pneumococcal disease.
• Auranofin-loaded poly(lactic-co-glycolic acid (PLGA) nanoparticles showed a strong bactericidal effect against multiresistant pneumococcal strains on planktonic cultures, biofilms and in a zebrafish embryo model. Auranofin PLGA nanocarriers showed enhanced bactericidal activity compared to the free drug.
• Immunization with the peptidoglycan hydrolase LytB elicits IgGs of different subclasses that activates complement-mediated phagocytosis. Vaccination with LytB increased bacterial clearance and induced protection in animal models.
• A novel chimeric N-acetylmuramoyl-L-alanine amidase (PL3) was constructed by fusing the catalytic domain of the Pal amidase to the CBD of the LytA autolysin. Low doses of PL3 practically sterilized the cultures of streptococci of the mitis group. PL3, remained active when stored at 37°C and after lyophilization, and showed full protection against pneumococci-infected zebrafish embryos.
• The relevance of the diiA gene in pneumococcal pathogenesis was investigated. Mutants lacking diiA were less efficient in nasopharyngeal colonization and dissemination from lungs, and suffered a severe impairment in blood proliferation. Purified DiiA bound to collagen and lactoferrin with high affinity.
• Non-typeable Haemophilus influenzae (NTHi) forms biofilms in vitro, producing an extracellular matrix composed of proteins, nucleic acids, and a ß-glucan. Extracellular nucleic acids are essential in biofilm formation and maintenance. The matrix polysaccharide contains residues of Glcp(1->4). N-acetyl-L- cysteine killed in vitro NTHi biofilms.
• In 2016, the patent entitled “Detection of Streptococcus pneumoniae through magneto-amperometric genosensors employing specific primers and probes for the lytA gene” was approved both in USA and in the EU.
• María Soledad Escolano and Roberto Vázquez received awards for their oral presentation and poster communication, respectively, in the Jornadas de Formación del CIBERES (2016).
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