Person:
Martín Brieva, Humberto

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First Name
Humberto
Last Name
Martín Brieva
URI
https://hdl.handle.net/20.500.14352/77676
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Microbiología y Parasitología
Area
Microbiología
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2018 - 201912020 - 20211
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    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, Humberto
    Azoles 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.
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    Educating in antimicrobial resistance awareness: adaptation of the Small World Initiative program to service-learning.
    (FEMS Microbiology Letters, 2018) Valderrama Conde, María José; González Zorn, Bruno; Calvo De Pablo, Pilar; Díez Orejas, Rosalía María; Fernández-Acero Bascones, Teresa; Gil Serna, Jessica; Juan Ferré, Lucía De; Martín Brieva, Humberto; Molina Martín, María; Navarro García, Federico; Patiño Álvarez, Aurora Belén; Pla Alonso, Jesús; Prieto, Daniel; Rodríguez Fernández, Carmina; Román González, Elvira; Sanz Santamaría, Ana Belén; Silóniz Jiménez, María Isabel De; Suárez Rodríguez, Mónica; Vázquez Estévez, María Covadonga Inmaculada; Jiménez Cid, Víctor
    The Small World Initiative (SWI) and Tiny Earth are a consolidated and successful education programs rooted in the USA that tackle the antibiotic crisis by a crowdsourcing strategy. Based on active learning, it challenges young students to discover novel bioactive-producing microorganisms from environmental soil samples. Besides its pedagogical efficiency to impart microbiology content in academic curricula, SWI promotes vocations in research and development in Experimental Sciences and, at the same time, disseminates the antibiotic awareness guidelines of the World Health Organization. We have adapted the SWI program to the Spanish academic environment by a pioneering hierarchic strategy based on service-learning that involves two education levels (higher education and high school) with different degrees of responsibility. Throughout the academic year, 23 SWI teams, each consisting of 3-7 undergraduate students led by one faculty member, coordinated off-campus programs in 22 local high schools, involving 597 high school students as researchers. Post-survey-based evaluation of the program reveals a satisfactory achievement of goals: acquiring scientific abilities and general or personal competences by university students, as well as promoting academic decisions to inspire vocations for science- and technology-oriented degrees in younger students, and successfully communicating scientific culture in antimicrobial resistance to a young stratum of society.