Person: Molina Martín, María
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First Name
María
Last Name
Molina Martín
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Microbiología y Parasitología
Area
Microbiología
Identifiers
11 results
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Item MicroMundo: una aproximación a la perspectiva One Health de Salud Global mediante Aprendizaje-Servicio integrando diversos niveles educativos(2022) González Zorn, Bruno; Román González, Elvira; Molina Martín, María; Martín Brieva, Humberto; Escudero García-Calderón, José Antonio; Rodríguez Fernández, Carmina; Bezos Garrido, Javier; Álvarez Sánchez, Julio; Pérez Sancho, Marta; Amaro Torres, Francisco; Jiménez Cid, Víctor; Suárez Rodríguez, Mónica; Patiño Álvarez, Aurora Belén; Calvo De Pablo, Pilar; Fernández-Acero Bascones, Teresa; Pavón Verges, Mónica; Sanz Santamaría, Ana Belén; Díaz Del Toro, Silvia; González Rubio, Gema; Vázquez Estévez, María Covadonga Inmaculada; Gil Serna, Jessica; Jiménez Gutiérrez, Elena; Del Val Oriza, Elba; Valentí Sanguino, Marta; Sellers Moya, Ángela; Sastre Vergara, LucíaMicroMundo es la adaptación a Aprendizaje-Servicio (ApS) de la estrategia de crowdsourcing y ciencia ciudadana internacional Tiny Earth. Su objetivo de servicio esencial es acercar la cultura científica, la perspectiva One Health y la investigación biomédica a la sociedad, poniendo el foco en jóvenes estudiantes para fomentar la vocación por formación en Grados STEM y por la investigación. La pandemia de COVID-19 y sus consecuencias han puesto de manifiesto la urgencia de acercar la cultura científica en el ámbito de la Biomedicina y la Salud Pública a la sociedad e implicar en esta tarea a nuestros estudiantes. Pero también la pandemia ha impuesto cambios en nuestro esquema de trabajo durante este curso, lo que nos ha obligado a trabajar on-line en lugar de llevar a cabo las características actividades experimentales de aprendizaje activo en las que se fundamenta el proyecto en condiciones normales. Manteniendo los mismos objetivos, las intervenciones en los 20 Colegios e Institutos en los que hemos realizado el proyecto se han enfocado en la elaboración de materiales divulgativos e intervenciones en la comunidad por parte de los jóvenes estudiantes, de manera coordinada por nuestros estudiantes universitarios y la organización de un Simposio on-line de ámbito nacional donde se expusieron y compartieron las diversas iniciativas. La elevada participación en el Simposio, de inscripción gratuita (más de 500 inscritos) y la calidad de las 69 ponencias propuestas, la mayoría de manera conjunta por alumnos de instituto y universitarios, avala el enorme éxito de la iniciativa virtual y la consecución de objetivos. El material generado (videojuegos, entornos educativos virtuales, paisajes de aprendizaje, escape rooms, videos, campañas en Instagram o Tik Tok, blogs, etc) será muy valioso como material de apoyo en sucesivas ediciones de MicroMundo. Todo este material se irá divulgando en el portal www.esmisionposible.com las redes sociales @EsMisionPosible, gestionados por el proyecto. En resumen, consideramos que nuestro proyecto que implica tanto a estudiantes y profesores de centros educativos de Educación Secundaria y Bachillerato en la CAM a, como a profesores y estudiantes universitarios de los ámbitos de Sanidad Humana, Animal y Medioambiental de manera transversal e interfacultativa, ha afrontado con éxito el reto de adaptar el proyecto a la situación epidemiológica, reforzándolo con actividades no presenciales orientadas a consolidar una comunidad MicroMundo virtual en la que los estudiantes pueden compartir sus experiencias en la divulgación del problema de la resistencia y el fomento de la investigación para el descubrimiento de nuevos antimicrobianos.Item MicroMundo: Ciencia Ciudadana para el descubrimiento y concienciación sobre el uso de antibióticos mediante Aprendizaje-Servicio(2020) Jiménez Cid, Víctor; Calvo De Pablo, Pilar; Román González, Elvira; Patiño Álvarez, Aurora Belén; González Zorn, Bruno; Gómez-Luz Centellés, María Luisa; Molina Martín, María; Martín Brieva, Humberto; Escudero García-Calderón, José Antonio; Pavón Verges, Mónica; Rodríguez Fernández, Carmina; Díaz Del Toro, Silvia; Rodríguez Escudero, María Isabel; Vázquez Estévez, María Covadonga Inmaculada; Bezos Garrido, Javier; Álvarez Sánchez, Julio; Amaro Torres, Francisco; Suárez Rodríguez, Mónica; Gil Serna, Jessica; Fernández-Acero Bascones, Teresa; Sanz Santamaría, Ana Belén; González Rubio, Gema; Jiménez Gutiérrez, Elena; Coronas Serna, Julia María; Valentí Sanguino, Marta; Del Val Oriza, Elba; Sellers Moya, Ángela; Gibello Prieto, Alicia; Arias López, Patricia; Sastre Vergara, LucíaMicroMundo es un proyecto de Ciencia Ciudadana basado en aprendizaje activo, en el que estudiantes de ESO y Bachillerato, objeto del servicio, coordinados por equipos de estudiantes universitarios, objeto del aprendizaje, desarrollan un proyecto de investigación real. El objetivo de la investigación es el aislamiento, a partir de microorganismos de muestras de suelo, de nuevas actividades antibióticas. Los objetivos de servicio son acercar cultura científica a la sociedad en Salud Global, con foco en el problema de la resistencia a antibióticos, actuando sobre la población más joven,al tiempo que se crean en ellos vocaciones STEM y curiosidad por la I+D en Biomedicina. Durante el curso 2019-20, 150 nuevos alumnos se han incorporado al proyecto interfacultativo en la UCM, trabajando en 26 centros educativos de la Comunidad de Madrid. El confinamiento por la situación pandémica ha reforzado el interés del proyecto, pero ha obligado a pasar el entorno on-line algunas de las actuaciones previstas. No obstante, los objetivos del proyecto se han alcanzado.Item The TIR-domain containing effectors BtpA and BtpB from Brucella abortus impact NAD metabolism(Plos Pathogens, 2020) Coronas Serna, Julia María; Louche, Arthur; Roussin, Morgane; Imbert, Paul RC; Rodríguez Escudero, María Isabel; Terradot, laurent; Molina Martín, María; Gorvel, Jean-Pierre; Jiménez Cid, Víctor; Salcedo, Suzana P; Rodríguez-Escudero, IsabelBrucella species are facultative intracellular Gram-negative bacteria relevant to animal and human health. Their ability to establish an intracellular niche and subvert host cell pathways to their advantage depends on the delivery of bacterial effector proteins through a type IV secretion system. Brucella Toll/Interleukin-1 Receptor (TIR)-domain-containing proteins BtpA (also known as TcpB) and BtpB are among such effectors. Although divergent in primary sequence, they interfere with Toll-like receptor (TLR) signaling to inhibit the innate immune responses. However, the molecular mechanisms implicated still remain unclear. To gain insight into the functions of BtpA and BtpB, we expressed them in the budding yeast Saccharomyces cerevisiae as a eukaryotic cell model. We found that both effectors were cytotoxic and that their respective TIR domains were necessary and sufficient for yeast growth inhibition. Growth arrest was concomitant with actin depolymerization, endocytic block and a general decrease in kinase activity in the cell, suggesting a failure in energetic metabolism. Indeed, levels of ATP and NAD+ were low in yeast cells expressing BtpA and BtpB TIR domains, consistent with the recently described enzymatic activity of some TIR domains as NAD+ hydrolases. In human epithelial cells, both BtpA and BtpB expression reduced intracellular total NAD levels. In infected cells, both BtpA and BtpB contributed to reduction of total NAD, indicating that their NAD+ hydrolase functions are active intracellularly during infection. Overall, combining the yeast model together with mammalian cells and infection studies our results show that BtpA and BtpB modulate energy metabolism in host cells through NAD+ hydrolysis, assigning a novel role for these TIR domain-containing effectors in Brucella pathogenesis.Item Micromundo@ucm: investigación y concienciación contra la pandemia silenciosa de la resistencia a antibióticos(2022) Gómez Albarrán, Carolina; Amaro Torres, Francisco; Molina Martín, María; Jiménez Gutiérrez, Elena; Sellers Moya, Ángela; Gil Serna, Jessica; González Rubio, Gema; De Francisco Martínez, Patricia; Prieto Orzanco, Alicia María; González de Figueras, Carolina; Fernández-Acero Bascones, Teresa; Román González, Elvira; Calvo De Pablo, Pilar; Vázquez Estévez, María Covadonga Inmaculada; Rodríguez Fernández, Carmina; Sempere García, Julio; Domenech Lucas, Mirian; Serna Bernaldo, Carlos; Díaz Del Toro, Silvia; Patiño Álvarez, Aurora Belén; Blanco Torres, Paula; Valdés González, José Antonio; Rubio Lozano, Alba Victoria; Lavilla García, Beatriz; Del Val Oriza, Elba; Romero Martínez, Beatriz; Valentí Sanguino, Marta; López Montesino, Sara; Martínez López, Raquel María; Escudero García-Calderón, José Antonio; Sastre Vergara, Lucía; García Pastor, Lucía; Pérez Sancho, Marta; Kieffer, Nicolas; Bezos Garrido, Javier; Hipólito Carrillo de Albornoz, Alberto; Muñoz Atienza, Estefanía; Trigo da Roza, Filipa; Suárez Rodríguez, Mónica; García Bezanquen, Nerea; Marín Martínez, María; Vergara González, Ester; González Zorn, Bruno; Borrero Del Pino, Juan; Jiménez Cid, Víctor; Maestro García-Donas, María BeatrizActualmente se estima que las resistencias antibióticas se cobran 1.270.000 vidas anualmente a nivel global. Es necesario contribuir desde multiples ángulos a preservar la efectividad de os antibióticos y descubrir nuevas etsrategias terapéuticas. MicroMundo es un proyecto de Aprendizaje-Servicio y Ciencia Ciudadana que pretende crear cultura científica y concienciación en cuestiones de Salud Global en los jóvenes. Se pretende que sean los más jóvenes, los estudiantes de ESO y Bachillerato, los responsables de la transmisión de ese conocimiento a la comunidad. Pero un segundo objetivo, no menos importante, es el de generar y potenciar vocaciones STEM e interés por el I+D en Biomedicina. Para conseguir estos objetivos, diversos equipos de estudiantes universitarios imparten y coordinan el proyecto en colegios e institutos de su comunidad, coordinados por sus tutores (profesores e investigadores del área de Microbiología de las Facultades de Farmacia, Medicina, Veterinaria y Biología, cubriendo los tres vértices del triángulo One Health: salud humana, animal y medioambiental). En la UCM, durante el curso 2021-22, treinta y dos equipos de han trabajado en unos treinta colegios e institutos, implicando a unos 600 estudiantes preuniversitarios en el trabajo experimental del proyecto.Item Functional analysis of PTEN variants of unknown significance from PHTS patients unveils complex patterns of PTEN biological activity in disease(Eur J Hum Genet., 2023) Torices, Leire; Mingo, Janire; Rodríguez Escudero, María Isabel; Fernández-Acero Bascones, Teresa; Luna, Sandra; Nunes-Xavier, Caroline E.; López, José I.; Mercadillo, Fátima; Currás, María; Urioste, Miguel; Molina Martín, María; Jiménez Cid, Víctor; Pulido, RafaelHeterozygous germline mutations in PTEN gene predispose to hamartomas and tumors in different tissues, as well as to neurodevelopmental disorders, and define at genetic level the PTEN Hamartoma Tumor Syndrome (PHTS). The major physiologic role of PTEN protein is the dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3), counteracting the pro-oncogenic function of phosphatidylinositol 3-kinase (PI3K), and PTEN mutations in PHTS patients frequently abrogate PTEN PIP3 catalytic activity. PTEN also displays non-canonical PIP3-independent functions, but their involvement in PHTS pathogeny is less understood. We have previously identified and described, at clinical and genetic level, novel PTEN variants of unknown functional significance in PHTS patients. Here, we have performed an extensive functional characterization of these PTEN variants (c.77 C > T, p.(Thr26Ile), T26I; c.284 C > G, p.(Pro95Arg), P95R; c.529 T > A, p.(Tyr177Asn), Y177N; c.781 C > G, p.(Gln261Glu), Q261E; c.829 A > G, p.(Thr277Ala), T277A; and c.929 A > G, p.(Asp310Gly), D310G), including cell expression levels and protein stability, PIP3-phosphatase activity, and subcellular localization. In addition, caspase-3 cleavage analysis in cells has been assessed using a C2-domain caspase-3 cleavage-specific anti-PTEN antibody. We have found complex patterns of functional activity on PTEN variants, ranging from loss of PIP3-phosphatase activity, diminished protein expression and stability, and altered nuclear/cytoplasmic localization, to intact functional properties, when compared with PTEN wild type. Furthermore, we have found that PTEN cleavage at the C2-domain by the pro-apoptotic protease caspase-3 is diminished in specific PTEN PHTS variants. Our findings illustrate the multifaceted molecular features of pathogenic PTEN protein variants, which could account for the complexity in the genotype/phenotype manifestations of PHTS patients.Item A global analysis of the reconstitution of PTEN function by translational readthrough of PTEN pathogenic premature termination codons(Human mutation, 2021) Luna, Sandra; Torices, Leire; Mingo, Janire; Amo, Laura; Ruiz‐Ibarlucea, Pablo; Erramuzpe, Asier; Cortés, Jesús M.; Tejada, María I.; Nunes‐Xavier, Caroline E.; López, José I.; Pulido, Rafael; Rodríguez Escudero, María Isabel; Jiménez Cid, Víctor; Molina Martín, MaríaThe PTEN tumor suppressor gene is mutated with high incidence in tumors and in thegermline of patients with cancer predisposition or with macrocephaly associatedwith autism.PTENnonsense mutations generating premature termination codons (PTC)and producing nonfunctional truncated PTEN proteins are frequent in association withhuman disease. However, there are no studies addressing the restoration of full‐lengthPTEN proteins from the PTC‐mutatedPTENgene by translational readthrough. Here,we have performed a global translational and functional readthrough analysis of thecomplete collection ofPTENPTC somatic or hereditary mutations found in tumors or inthegermlineofpatients(disease‐associated PTEN PTCome), and we set standards forthe analysis of the potential of readthrough functional reconstitution in disease‐relevant genes. Our analysis indicates that prevalent pathogenicPTENPTC mutationsare susceptible to PTEN functional restoration in response to readthrough‐inducingcompounds. Comprehensive readthrough analyses of disease‐associated PTComes willbe valuable tools for the implementation of readthrough‐based precision interventionsin specific groups of patientsItem Differential Role of Threonine and Tyrosine Phosphorylation in the Activation and Activity of the Yeast MAPK Slt2(International Journal of Molecular Sciences, 2021) González Rubio, Gema; Sellers Moya, Ángela; Martín Brieva, Humberto; Molina Martín, MaríaThe Mitogen-Activated Protein Kinase (MAPK) Slt2 is central to signaling through the yeast Cell Wall Integrity (CWI) pathway. MAPKs are regulated by phosphorylation at both the threonine and tyrosine of the conserved TXY motif within the activation loop (T190/Y192 in Slt2). Since phosphorylation at both sites results in the full activation of MAPKs, signaling through MAPK pathways is monitored with antibodies that detect dually phosphorylated forms. However, most of these antibodies also recognize monophosphorylated species, whose relative abundance and functionality are diverse. By using different phosphospecific antibodies and phosphate-affinity (Phostag) analysis on distinct Slt2 mutants, we determined that Y192- and T190-monophosphorylated species coexist with biphosphorylated Slt2, although most of the Slt2 pool remains unphosphorylated following stress. Among the monophosphorylated forms, only T190 exhibited biological activity. Upon stimulation, Slt2 is first phosphorylated at Y192, mainly by the MAPKK Mkk1, and this phosphorylation is important for the subsequent T190 phosphorylation. Similarly, dephosphorylation of Slt2 by the Dual Specificity Phosphatase (DSP) Msg5 is ordered, with dephosphorylation of T190 depending on previous Y192 dephosphorylation. Whereas Y192 phosphorylation enhances the Slt2 catalytic activity, T190 is essential for this activity. The conserved T195 residue is also critical for Slt2 functionality. Mutations that abolish the activity of Slt2 result in a high increase in inactive Y192- monophosphorylated Slt2. The coexistence of different Slt2 phosphoforms with diverse biological significance highlights the importance of the precise detection of the Slt2 phosphorylation status.Item Clotrimazole-Induced Oxidative Stress Triggers Novel Yeast Pkc1-Independent Cell Wall Integrity MAPK Pathway Circuitry(Journal of Fungi, 2021) Sellers Moya, Ángela; Nuévalos, Marcos; Molina Martín, María; Martín Brieva, HumbertoAzoles are one of the most widely used drugs to treat fungal infections. To further understand the fungal response to azoles, we analyzed the MAPK circuitry of the model yeast Saccharomyces cerevisiae that operates under treatment with these antifungals. Imidazoles, and particularly clotrimazole, trigger deeper changes in MAPK phosphorylation than triazoles, involving a reduction in signaling through the mating pathway and the activation of the MAPKs Hog1 and Slt2 from the High-Osmolarity Glycerol (HOG) and the Cell Wall Integrity (CWI) pathways, respectively. Clotrimazole treatment leads to actin aggregation, mitochondrial alteration, and oxidative stress, which is essential not only for the activation of both MAPKs, but also for the appearance of a low-mobility form of Slt2 caused by additional phosphorylation to that occurring at the conserved TEY activation motif. Clotrimazole-induced ROS production and Slt2 phosphorylation are linked to Tpk3-mediated PKA activity. Resistance to clotrimazole depends on HOG and CWI-pathway-mediated stress responses. However, Pkc1 and other proteins acting upstream in the pathway are not critical for the activation of the Slt2 MAPK module, suggesting a novel rewiring of signaling through the CWI pathway. We further show that the strong impact of azole treatment on MAPK signaling is conserved in other yeast species.Item Klebsiella pneumoniae type VI secretion system-mediated microbial competition is PhoPQ controlled and reactive oxygen species dependent(Plos pathogens, 2020) Storey, Daniel; McNally, Allan; Astrand, Mia; Sa-Pessoa Graca Santos, Joana; Rodriguez-escudero, Isabel; Elmore, Bronagh; Palacios, leyre; Marshall, Helina; Hobley, Laura; Molina, Maria; Iiménez Cid, Victor; Salminen, Tiina A; Bengoechea, Jose A; Molina Martín, María; Rodríguez Escudero, María Isabel; Molina, Maria; Jiménez Cid, Víctor; Molina Martín, MaríaKlebsiella pneumoniae is recognized as an urgent threat to human health due to the increasing isolation of multidrug resistant strains. Hypervirulent strains are a major concern due to their ability to cause life-threating infections in healthy hosts. The type VI secretion system (T6SS) is widely implicated in microbial antagonism, and it mediates interactions with host eukaryotic cells in some cases. In silico search for genes orthologous to T6SS component genes and T6SS effector genes across 700 K. pneumoniae genomes shows extensive diversity in T6SS genes across the K. pneumoniae species. Temperature, oxygen tension, pH, osmolarity, iron levels, and NaCl regulate the expression of the T6SS encoded by a hypervirulent K. pneumoniae strain. Polymyxins and human defensin 3 also increase the activity of the T6SS. A screen for regulators governing T6SS uncover the correlation between the transcription of the T6SS and the ability to kill E. coli prey. Whereas H-NS represses the T6SS, PhoPQ, PmrAB, Hfq, Fur, RpoS and RpoN positively regulate the T6SS. K. pneumoniae T6SS mediates intra and inter species bacterial competition. This antagonism is only evident when the prey possesses an active T6SS. The PhoPQ two component system governs the activation of K. pneumoniae T6SS in bacterial competitions. Mechanistically, PhoQ periplasmic domain, and the acid patch within, is essential to activate K. pneumoniae T6SS. Klebsiella T6SS also mediates anti-fungal competition. We have delineated the contribution of each of the individual VgrGs in microbial competition and identified VgrG4 as a T6SS effector. The DUF2345 domain of VgrG4 is sufficient to intoxicate bacteria and yeast. ROS generation mediates the antibacterial effects of VgrG4, and the antitoxin Sel1E protects against the toxic activity of VgrG4. Our findings provide a better understanding of the regulation of the T6SS in bacterial competitions, and place ROS as an early event in microbial competition.Item A trans-kingdom T6SS effector induces the fragmentation of the mitochondrial network and activates innate immune receptor NLRX1 to promote infection(Nat. Commun., 2023) Sá-Pessoa, Joana; López-Montesino, Sara; Przybyszewska, Kornelia; Marshall, Helina; Ova, Adelia; Schroeder, Gunnar N; Barabas, Peter; Curtis, Tim; Bengoechea, Jose A; Rodríguez Escudero, María Isabel; Jiménez Cid, Víctor; Molina Martín, MaríaBacteria can inhibit the growth of other bacteria by injecting effectors using a type VI secretion system (T6SS). T6SS effectors can also be injected into eukaryotic cells to facilitate bacterial survival, often by targeting the cytoskeleton. Here, we show that the trans-kingdom antimicrobial T6SS effector VgrG4 from Klebsiella pneumoniae triggers the fragmentation of the mitochondrial network. VgrG4 colocalizes with the endoplasmic reticulum (ER) protein mitofusin 2. VgrG4 induces the transfer of Ca2+ from the ER to the mitochondria, activating Drp1 (a regulator of mitochondrial fission) thus leading to mitochondrial network fragmentation. Ca2+ elevation also induces the activation of the innate immunity receptor NLRX1 to produce reactive oxygen species (ROS). NLRX1-induced ROS limits NF-κB activation by modulating the degradation of the NF-κB inhibitor IκBα. The degradation of IκBα is triggered by the ubiquitin ligase SCFβ-TrCP, which requires the modification of the cullin-1 subunit by NEDD8. VgrG4 abrogates the NEDDylation of cullin-1 by inactivation of Ubc12, the NEDD8-conjugating enzyme. Our work provides an example of T6SS manipulation of eukaryotic cells via alteration of the mitochondria.