https://hdl.handle.net/10259/4862 2026-04-18T14:40:33Z 2026-04-18T14:40:33Z Antón Fidalgo, Nuria Mendes, Marta V. Martín, Juan F. Aparicio, Jesús F. https://hdl.handle.net/10259/11321 2026-02-05T01:05:55Z 2004-05-01T00:00:00Z

Identification of PimR as a Positive Regulator of Pimaricin Biosynthesis in Streptomyces natalensis Antón Fidalgo, Nuria; Mendes, Marta V.; Martín, Juan F.; Aparicio, Jesús F. Sequencing of the DNA region on the left fringe of the pimaricin gene cluster revealed the presence of a 3.6-kb gene, pimR, whose deduced product (1,198 amino acid residues) was found to have amino acid sequence homology with bacterial regulatory proteins. Database comparisons revealed that PimR represents the archetype of a new class of regulators, combining a Streptomyces antibiotic regulatory protein (SARP)-like N-terminal section with a C-terminal half homologous to guanylate cyclases and large ATP-binding regulators of the LuxR family. Gene replacement of pimR from Streptomyces natalensis chromosome results in a complete loss of pimaricin production, suggesting that PimR is a positive regulator of pimaricin biosynthesis. Gene expression analysis by reverse transcriptase PCR (RT-PCR) of the pimaricin gene cluster revealed that S. natalensis ΔPimR shows no expression at all of the cholesterol oxidase-encoding gene pimE, and very low level transcription of the remaining genes of the cluster except for the mutant pimR gene, thus demonstrating that this regulator activates the transcription of all the genes belonging to the pimaricin gene cluster but not its own transcription.

2004-05-01T00:00:00Z Aparicio Fernández, Jesús Manuel Mendes, Marta V. Antón Fidalgo, Nuria Martín Martín, Juan Francisco https://hdl.handle.net/10259/11297 2026-01-28T01:05:45Z 2002-01-01T00:00:00Z

Biosynthetic rules for marcrolide construction Aparicio Fernández, Jesús Manuel; Mendes, Marta V.; Antón Fidalgo, Nuria; Martín Martín, Juan Francisco Macrolides constitute a large class of natural metabolites produced by giant multifunctional enzymes in a process resembling fatty acid biosynthesis. Like f atty acids, macrolides and other polyketides are assernbled by decarboxylative condensations of simple carboxylic acids. But while fatty acid intermediates are fully reduced, macrolide and other polyketide intermediates suffer the suppression of reduction or dehydration reactions at given biosynthetic steps. In the last years much progress has 'been made in our understanding of the linear and modular organisation of the gene clusters, and the enzymes encoded by them, responsiblefor...

2002-01-01T00:00:00Z Fernandez Becerra, Carmen Lelievre, Joel Ferrer, Mireia Antón Fidalgo, Nuria Thomson, Richard Peligero, Cristina Almela, Maria Jesus Lacerda, Marcus VG Herreros, Esperanza del Portillo, Hernando A https://hdl.handle.net/10259/11295 2026-01-28T01:05:46Z 2013-09-01T00:00:00Z

Red blood cells derived from peripheral blood and bone marrow CD34+ human haematopoietic stem cells are permissive to Plasmodium parasites infection Fernandez Becerra, Carmen; Lelievre, Joel; Ferrer, Mireia; Antón Fidalgo, Nuria; Thomson, Richard; Peligero, Cristina; Almela, Maria Jesus; Lacerda, Marcus VG; Herreros, Esperanza; del Portillo, Hernando A The production of fully functional human red cells in vitro from haematopoietic stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs from cord blood represented a major improvement to develop the continuous culture system for Plasmodium vivax. Here, we demonstrated that CD34+ hHSCs from peripheral blood and bone marrow can be expanded and differentiated to reticulocytes using a novel stromal cell. Moreover, these reticulocytes and mature red blood cells express surface markers for entrance of malaria parasites contain adult haemoglobin and are also permissive to invasion by P. vivax and Plasmodium falciparum parasites.

2013-09-01T00:00:00Z Arunkumar, Guha Asthagiri Ioannou, Andriani Wohlbold, Teddy John Meade, Philip Aslam, Sadaf Amanat, Fatima Ayllón Barasoain, Juan García Sastre, Adolfo Krammer, Florian https://hdl.handle.net/10259/10928 2025-10-07T11:19:39Z 2019-03-01T00:00:00Z

Broadly Cross-Reactive, Nonneutralizing Antibodies against Influenza B Virus Hemagglutinin Demonstrate Effector Function-Dependent Protection against Lethal Viral Challenge in Mice Arunkumar, Guha Asthagiri; Ioannou, Andriani; Wohlbold, Teddy John; Meade, Philip; Aslam, Sadaf; Amanat, Fatima; Ayllón Barasoain, Juan; García Sastre, Adolfo; Krammer, Florian Protection from influenza virus infection is canonically associated with antibodies that neutralize the virus by blocking the interaction between the viral hemagglutinin and host cell receptors. However, protection can also be conferred by other mechanisms, including antibody-mediated effector functions. Here, we report the characterization of 22 broadly cross-reactive, nonneutralizing antibodies specific for influenza B virus hemagglutinin. The majority of these antibodies recognized influenza B viruses isolated over the period of 73 years and bind the conserved stalk domain of the hemagglutinin. A proportion of the characterized antibodies protected mice from both morbidity and mortality after challenge with a lethal dose of influenza B virus. Activity in an antibody-dependent cell-mediated cytotoxicity reporter assay correlated strongly with protection, suggesting that Fc-dependent effector function determines protective efficacy. The information regarding mechanism of action and epitope location stemming from our characterization of these antibodies will inform the design of urgently needed vaccines that could induce broad protection against influenza B viruses.

2019-03-01T00:00:00Z