Person:
Rodríguez Peña, José Manuel

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First Name
José Manuel
Last Name
Rodríguez Peña
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Microbiología y Parasitología
Area
Microbiología
Identifiers
UCM identifierORCIDScopus Author IDWeb of Science ResearcherIDDialnet IDGoogle Scholar ID

Search Results

Now showing 1 - 10 of 10
  • Publication
    Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature.
    (BioMed Central, 2015-09-05) García Sánchez, Raúl; Botet, Javier; Rodríguez Peña, José Manuel; Bermejo, Clara; Ribas, Juan Carlos; Revuelta, José Luis; Nombela, César; Arroyo, Javier
    BACKGROUND The fungal cell wall forms a compact network whose integrity is essential for cell morphology and viability. Thus, fungal cells have evolved mechanisms to elicit adequate adaptive responses when cell wall integrity (CWI) is compromised. Functional genomic approaches provide a unique opportunity to globally characterize these adaptive mechanisms. To provide a global perspective on these CWI regulatory mechanisms, we developed chemical-genomic profiling of haploid mutant budding yeast cells to systematically identify in parallel those genes required to cope with stresses interfering the cell wall by different modes of action: β-1,3 glucanase and chitinase activities (zymolyase), inhibition of β-1,3 glucan synthase (caspofungin) and binding to chitin (Congo red). RESULTS Measurement of the relative fitness of the whole collection of 4786 haploid budding yeast knock-out mutants identified 222 mutants hypersensitive to caspofungin, 154 mutants hypersensitive to zymolyase, and 446 mutants hypersensitive to Congo red. Functional profiling uncovered both common and specific requirements to cope with different cell wall damages. We identified a cluster of 43 genes highly important for the integrity of the cell wall as the common "signature of cell wall maintenance (CWM)". This cluster was enriched in genes related to vesicular trafficking and transport, cell wall remodeling and morphogenesis, transcription and chromatin remodeling, signal transduction and RNA metabolism. Although the CWI pathway is the main MAPK pathway regulating cell wall integrity, the collaboration with other signal transduction pathways like the HOG pathway and the invasive growth pathway is also required to cope with the cell wall damage depending on the nature of the stress. Finally, 25 mutant strains showed enhanced caspofungin resistance, including 13 that had not been previously identified. Only three of them, wsc1Δ, elo2Δ and elo3Δ, showed a significant decrease in β-1,3-glucan synthase activity. CONCLUSIONS This work provides a global perspective about the mechanisms involved in cell wall stress adaptive responses and the cellular functions required for cell wall integrity. The results may be useful to uncover new potential antifungal targets and develop efficient antifungal strategies by combination of two drugs, one targeting the cell wall and the other interfering with the adaptive mechanisms.
  • Publication
    The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast
    (MDPI, 2017-12-21) Sanz Santamaría, Ana Belén; García Sánchez, Raúl; Rodríguez Peña, José Manuel; Arroyo, Javier
    Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI) pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies.
  • Publication
    Diseño, desarrollo y elaboración de un soporte informático interactivo para el estudio de las prácticas de la asignatura de Microbiología Clínica mediante el uso de imágenes reales de pruebas microbiológicas obtenidas en el laboratorio
    (2020-06-01) Rodríguez Peña, José Manuel; Monteoliva Díaz, Lucía; Molero Martín-Portugués, María Gloria; Alonso Monge, Rebeca María del Mar; García Sánchez, Raúl; Amador García, Ahinara
    En las diferentes clases prácticas relacionadas con asignaturas de Microbiología, como sucede en otras áreas de conocimiento, un aspecto que requiere especial atención es el diseño y la elaboración de herramientas que contribuyan a facilitar y mejorar el aprendizaje por parte del alumnado de los múltiples conceptos microbiológicos que se imparten en las mismas, facilitando en lo posible la enseñanza no presencial. En este sentido, pensamos que la existencia de un soporte virtual interactivo de los distintos abordajes prácticos realizados en el laboratorio y sus posibles resultados facilitaría en gran medida el estudio, y por tanto, la adquisición de las competencias correspondientes a la docencia práctica de Microbiología. En los dos cursos académicos anteriores (2017/18 y 2018/19), a través de sendos proyectos UCM-INNOVA (Proyectos 161 y 76, respectivamente), se ha recopilado, con la participación activa de los alumnos, una gran cantidad de información gráfica de toda la labor práctica realizada durante la impartición de las asignaturas incluidas en diversas titulaciones, habiéndose generado de esta manera un amplio banco de imágenes de calidad para diversos usos docentes. El proyecto realizado (UCM-INNOVA 19/20 Proyecto 11), ha consistido en el diseño, generación e implementación de una herramienta informática en entorno PowerPoint, a la que hemos denominado EMC (Evaluación Microbiología Clínica), que pone en valor todo el esfuerzo realizado por parte del profesorado y los alumnos en los proyectos anteriores, en relación a la asignatura de Microbiología Clínica del 4º curso del Grado en Farmacia de la Universidad Complutense de Madrid. En la aplicación EMC se ha incluido y estructurado cada práctica concreta siguiendo la misma organización realizada en el laboratorio, donde se sigue una rutina secuencial y jerárquica en la que el alumno debe interpretar los resultados posibles, fundamentalmente presentados en formato gráfico, de cada una de las pruebas realizadas según el tipo/s de microorganismo/s implicados, siendo redirigido a otro panel de pruebas cada vez más específicas hasta completar cada una de las prácticas. Esta herramienta se ha mostrado útil, no sólo para facilitar el estudio y el aprendizaje de los contenidos temáticos prácticos, sino también para servir de soporte y complemento al estudio del programa teórico de la asignatura. Es importante destacar que, durante las prácticas de Microbiología Clínica se explican los síndromes clínicos relacionados con las enfermedades infecciosas más frecuentes y su diagnóstico microbiológico, incluyendo desde la obtención y procesamiento de las muestras biológicas problema, hasta su posterior análisis microbiológico diferencial con el objeto de identificar a los potenciales microorganismos patógenos responsables de cada cuadro. Tras la realización de cada práctica, las pruebas microbiológicas deben ser adecuadamente eliminadas, no pudiendo guardarse las pruebas de forma indefinida. Por lo tanto, poder revisitar cuantas veces sea necesario por el alumno todas las pruebas y sus correspondientes resultados e interpretación de forma sencilla y visual en un entorno amigable (tipo presentación PowerPoint), supone un apoyo al estudio y al aprendizaje. Finalmente, pensamos que es importante remarcar que incluso en Universidades donde la metodología docente es eminentemente presencial, el desarrollo y utilización de forma complementaria de herramientas que faciliten el aprendizaje on-line es crucial en los tiempos que vivimos, cómo ha dejado patente la pandemia de la COVID-19.
  • Publication
    Control of Gene Expression via the Yeast CWI Pathway
    (MPDI, 2022-02-04) Sanz Santamaría, Ana Belén; García Sánchez, Raúl; Pavón Vergés, Mónica; Rodríguez Peña, José Manuel; Arroyo, Javier
    Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast Saccharomyces cerevisiae elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention.
  • Publication
    Implementación de informes de prácticas virtuales de Microbiología Clínica y construcción de un banco de imágenes para facilitar el aprendizaje de esta asignatura
    (2018-06-30) Monteoliva Díaz, Lucía; Molero Martín-Portugués, María Gloria; Rodríguez Peña, José Manuel; Alonso Monge, Rebeca María del Mar; García Sánchez, Raúl; Oliveira Vaz, Catarina
    El proyecto se ha desarrollado según lo previsto y se han alcanzado de manera muy satisfactoria los objetivos propuestos, generándose informes virtuales de prácticas de Microbiología Clínica de 4º de Farmacia y un banco de fotografías de pruebas microbiológicas. La realización de este proyecto ha resultado de gran interés para los estudiantes, repercutiendo además de forma positiva en sus calificaciones y no representando una carga de trabajo adicional excesiva. Para los profesores y otros miembros del equipo del proyecto también ha supuesto una experiencia muy gratificante y el material generado puede ahora tener múltiples aplicaciones docentes.
  • Publication
    Desarrollo de material audiovisual para la virtualización de prácticas de distintas asignaturas del área de Microbiología
    (2021-06) Alonso Monge, Rebeca María del Mar; Rodríguez Peña, José Manuel; Monteoliva Díaz, Lucía; Molero Martín-Portugués, María Gloria; Jiménez Gutiérrez, Elena; García Sánchez, Raúl
    Durante el desarrollo del proyecto innova 20-21 nº61 se ha generado material audiovisual para la enseñanza de conocimientos prácticos de asignaturas impartidas por el departamento de Microbiología y Parasitología de la Facultad de Farmacia. Se han generado 10 videos cortos (duración media de 4 minutos) para la asignatura de Microbiología e Inmunología del grado de Odontología y 4 videos más largos (de 7 a 18 minutos de duración) para la asignatura de Microbiología Industrial y Biotecnología del grado de Ciencia y Tecnología de los alimentos. Los videos se realizaron en las instalaciones del departamento por profesores implicados en ambas asignaturas. A continuación los videos fueron editados con un programa adquirido a propósito con el presupuesto del proyecto. El material se generó principalmente para poder implementar enseñanzas prácticas no presenciales y para reforzar el estudio autónomo de los estudiantes. Las encuestas a los alumnos revelaron una gran aceptación por parte de los alumnos con lo que se han cumplido los objetivos del proyecto.
  • Publication
    Poacic acid, a β‐1,3‐glucan–binding antifungal agent, inhibits cell‐wall remodeling and activates transcriptional responses regulated by the cell‐wall integrity and high‐osmolarity glycerol pathways in yeast
    (Federation of American Society of Experimental Biology (FASEB), 2021-08-12) García Sánchez, Raúl; Itto‐Nakama, Kaori; Rodríguez Peña, José Manuel; Chen, Xiaolin; Sanz Santamaría, Ana Belén; Lorenzo, Alba de; Pavón Vergés, Mónica; Kubo, Karen; Ohnuki, Shinsuke; Nombela Cano, César; Popolo, Laura; Ohya, Yoshikazu; Arroyo, Javier
    As a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits β-1,3-glucan synthesis in Saccharomyces cerevisiae and has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to β-1,3-glucan, its affinity for which is ~30-fold that for chitin. Besides its effect on β-1,3-glucan synthase activity, PA inhibited the yeast glucan-elongating activity of Gas1 and Gas2 and the chitin–glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co-regulation was mediated by parallel activation of the cell-wall integrity (CWI) and high-osmolarity glycerol signaling pathways. Despite targeting β-1,3-glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent.
  • Publication
    Cooperation between SAGA and SWI/SNF complexes is required for efficient transcriptional responses regulated by the yeast MAPK Slt2
    (Oxford Academic, 2016-09-06) Sanz Santamaría, Ana Belén; García Sánchez, Raúl; Rodríguez Peña, José Manuel; Nombela Cano, César; Arroyo Nombela, Francisco Javier
    The transcriptional response of Saccharomyces cerevisiae to cell wall stress is mainly mediated by the cell wall integrity (CWI) pathway through the MAPK Slt2 and the transcription factor Rlm1. Once activated, Rlm1 interacts with the chromatin remodeling SWI/SNF complex which locally alters nucleosome positioning at the target promoters. Here we show that the SAGA complex plays along with the SWI/SNF complex an important role for eliciting both early induction and sustained gene expression upon stress. Gcn5 co-regulates together with Swi3 the majority of the CWI transcriptional program, except for a group of genes which are only dependent on the SWI/SNF complex. SAGA subunits are recruited to the promoter of CWI-responsive genes in a Slt2, Rlm1 and SWI/SNF-dependent manner. However, Gcn5 mediates acetylation and nucleosome eviction only at the promoters of the SAGA-dependent genes. This process is not essential for pre-initiation transcriptional complex assembly but rather increase the extent of the remodeling mediated by SWI/SNF. As a consequence, H3 eviction and Rlm1 recruitment is completely blocked in a swi3Δ gcn5Δ double mutant. Therefore, SAGA complex, through its histone acetylase activity, cooperates with the SWI/SNF complex for the mandatory nucleosome displacement required for full gene expression through the CWI pathway.
  • Publication
    Chromatin remodeling by the SWI/SNF complex is essential for transcription mediated by the yeast cell wall integrity MAPK pathway.
    (2012-05-23) Sanz Santamaría, Ana Belén; García Sánchez, Raúl; Rodríguez Peña, José Manuel; Díez Muñiz, Sonia; Nombela Cano, César; Peterson, Craig L.; Arroyo Nombela, Francisco Javier
    In Saccharomyces cerevisiae, the transcriptional program triggered by cell wall stress is coordinated by Slt2/Mpk1, the mitogen-activated protein kinase (MAPK) of the cell wall integrity (CWI) pathway, and is mostly mediated by the transcription factor Rlm1. Here we show that the SWI/SNF chromatin-remodeling complex plays a critical role in orchestrating the transcriptional response regulated by Rlm1. swi/snf mutants show drastically reduced expression of cell wall stress-responsive genes and hypersensitivity to cell wall-interfering compounds. On stress, binding of RNA Pol II to the promoters of these genes depends on Rlm1, Slt2, and SWI/SNF. Rlm1 physically interacts with SWI/SNF to direct its association to target promoters. Finally, we observe nucleosome displacement at the CWI-responsive gene MLP1/KDX1, which relies on the SWI/SNF complex. Taken together, our results identify the SWI/SNF complex as a key element of the CWI MAPK pathway that mediates the chromatin remodeling necessary for adequate transcriptional response to cell wall stress.
  • Publication
    Rlm1 mediates positive autoregulatory transcriptional feedback that is essential for Slt2-dependent gene expression
    (The Company of Biologists, 2016-04-15) García Sánchez, Raúl; Sanz Santamaría, Ana Belén; Nombela Cano, César; Rodríguez Peña, José Manuel; Arroyo Nombela, Francisco Javier
    Activation of the yeast cell wall integrity (CWI) pathway induces an adaptive transcriptional programme that is largely dependent on the transcription factor Rlm1 and the mitogen-activated protein kinase (MAPK) Slt2. Upon cell wall stress, the transcription factor Rlm1 is recruited to the promoters of RLM1 and SLT2, and exerts positive-feedback mechanisms on the expression of both genes. Activation of the MAPK Slt2 by cell wall stress is not impaired in strains with individual blockade of any of the two feedback pathways. Abrogation of the autoregulatory feedback mechanism on RLM1 severely affects the transcriptional response elicited by activation of the CWI pathway. In contrast, a positive trans-acting feedback mechanism exerted by Rlm1 on SLT2 also regulates CWI output responses but to a lesser extent. Therefore, a complete CWI transcriptional response requires not only phosphorylation of Rlm1 by Slt2 but also concurrent SLT2- and RLM1-mediated positive-feedback mechanisms; sustained patterns of gene expression are mainly achieved by positive autoregulatory circuits based on the transcriptional activation of Rlm1.