Browsing by MeSH term "Antimicrobial Cationic Peptides"
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Publication Capsule enlargement in Cryptococcus neoformans confers resistance to oxidative stress suggesting a mechanism for intracellular survival(Wiley, 2008-10) Zaragoza, Oscar; Chrisman, Cara J; Castelli, Maria Victoria; Frases, Susana; Cuenca-Estrella, Manuel; Rodriguez-Tudela, Juan Luis; Casadevall, Arturo; Ministerio de Educación y Ciencia (España); Instituto de Salud Carlos IIICryptococcus neoformans is a facultative intracellular pathogen. The most distinctive feature of C. neoformans is a polysaccharide capsule that enlarges depending on environmental stimuli. The mechanism by which C. neoformans avoids killing during phagocytosis is unknown. We hypothesized that capsule growth conferred resistance to microbicidal molecules produced by the host during infection, particularly during phagocytosis. We observed that capsule enlargement conferred resistance to reactive oxygen species produced by H(2)O(2) that was not associated with a higher catalase activity, suggesting a new function for the capsule as a scavenger of reactive oxidative intermediates. Soluble capsular polysaccharide protected C. neoformans and Saccharomyces cerevisiae from killing by H(2)O(2). Acapsular mutants had higher susceptibility to free radicals. Capsular polysaccharide acted as an antioxidant in the nitroblue tetrazolium (NBT) reduction coupled to beta-nicotinamide adenine dinucleotide (NADH)/phenazine methosulfate (PMS) assay. Capsule enlargement conferred resistance to antimicrobial peptides and the antifungal drug Amphotericin B. Interestingly, the capsule had no effect on susceptibility to azoles and increased susceptibility to fluconazole. Capsule enlargement reduced phagocytosis by environmental predators, although we also noticed that in this system, starvation of C. neoformans cells produced resistance to phagocytosis. Our results suggest that capsular enlargement is a mechanism that enhances C. neoformans survival when ingested by phagocytic cells.Publication Chemical Reactivity Theory and Empirical Bioactivity Scores as Computational Peptidology Alternative Tools for the Study of Two Anticancer Peptides of Marine Origin(Multidisciplinary Digital Publishing Institute (MDPI), 2019-03-02) Frau, Juan; Flores-Holguin, Norma; Glossman-Mitnik, DanielThis work presents an account of the reactivity behavior of the anticancer marine drugs, Soblidotin and Tasidotin, based on the calculation of the global and local descriptors resulting from Chemical Reactivity Theory (CRT), also known as Conceptual DFT, for their consideration as a useful complement to approximations based on Molecular Docking. The information on the global and local reactivity descriptors of the Soblidotin and Tasidotin molecules, obtained through our proposed methodology, may be used for the design of new pharmaceutical analogs by relying on the chemical interactions between these peptides and their protein-type biological receptors. It can be concluded that the CRT approximation to the global and local chemical reactivity, based on the descriptors, can provide interesting information for the consideration of both molecules as potential therapeutic drugs. This is complemented by a study on Advanced Glycation Endproduct (AGE) inhibition, by comparison with the usual molecular systems considered for the task, as a re-purposing study. Finally, the bioactivity scores for Soblidotin and Tasidotin are predicted through an empirical procedure, based on comparison with molecular structures with well-known pharmacological properties.Publication Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense.(American Association for the Advancement of Science (AAAS), 2020-10) Bosch, Marta; Sanchez-Alvarez, Miguel; Fajardo, Alba; Kapetanovic, Ronan; Steiner, Bernhard; Dutra, Filipe; Moreira, Luciana; Lopez, Juan Antonio; Campo; Marí, Montserrat; Morales-Paytuví, Frederic; Tort, Olivia; Gubern, Albert; Templin, Rachel M; Curson, James E B; Martel, Nick; Català, Cristina; Lozano, Francisco; Tebar, Francesc; Enrich, Carlos; Vazquez, Jesus; del Pozo, Miguel Angel; Sweet, Matthew J; Bozza, Patricia T; Gross, Steven P; Parton, Robert G; Pol, Albert; Fundación La Marató TV3; Australian Research Council; Swiss National Science Foundation; National Health and Medical Research Council (Australia); Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Government of Catalonia (España); National Council for Scientific and Technological Development (Brasil); Worldwide Cancer Research; Fundación ProCNICLipid droplets (LDs) are the major lipid storage organelles of eukaryotic cells and a source of nutrients for intracellular pathogens. We demonstrate that mammalian LDs are endowed with a protein-mediated antimicrobial capacity, which is up-regulated by danger signals. In response to lipopolysaccharide (LPS), multiple host defense proteins, including interferon-inducible guanosine triphosphatases and the antimicrobial cathelicidin, assemble into complex clusters on LDs. LPS additionally promotes the physical and functional uncoupling of LDs from mitochondria, reducing fatty acid metabolism while increasing LD-bacterial contacts. Thus, LDs actively participate in mammalian innate immunity at two levels: They are both cell-autonomous organelles that organize and use immune proteins to kill intracellular pathogens as well as central players in the local and systemic metabolic adaptation to infection.