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Mechanisms and consequences of intracellular traffic impairment by 8- and 14-dehydrosterols in fungal parasite models

Grant number: 14/10443-0
Support Opportunities:Research Grants - Young Investigators Grants
Duration: August 01, 2015 - October 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Biochemistry of Microorganisms
Principal Investigator:Agustín Hernández López
Grantee:Agustín Hernández López
Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
Associated researchers: Aurelio Serrano Delgado ; Federico Valverde Albacete ; José María Romero Rodríguez ; José Román Pérez Castiñeira ; Maria Teresa Ruiz Pérez
Associated scholarship(s):16/07896-8 - Study of the mechanisms impairing cell wall maintenance by abnormal sterols in fungi, BP.MS
15/08436-8 - Mechanisms and consequences of intracellular traffic impairment by 8- and 14-dehydrosterols in fungal parasite models, BP.JP


Fungal parasites are among the most important pests affecting crop yields worldwide and are also the cause of some difficult to treat human diseases. In order to control pathogenic fungi, fungicides targeting the biosynthesis of ergosterol are widely used. However, the emergence of field resistances is hampering the efficacy of these compounds. Abnormal sterols of the kind accumulated by the effect of amine fungicides, or by mutations in the genes encoding ERG2 and ERG24 in yeast, have profound effects on endocytosis, cell wall maintenance, viability, lifespan and, probably, exocytosis. However, little is known about the molecular mechanisms behind these effects. Recently, inability to acidify lumina from endocellular organelles due to inhibition of the V-ATPase has been found as a common denominator in all these processes. The present project proposes the evaluation of the mechanisms by which V-ATPase inhibition by abnormal sterols brings about the above mentioned defects using Saccharomyces cerevisiae and Ustilago maydis as models for fungal parasites. The results obtained will help to understand the actual biocidal mechanisms of amine fungicides while providing valuable data towards the comprehension of the role of sterols in a cellular context. (AU)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CRISPIM, MARCELL; DAMASCENO, FLAVIA SILVA; HERNANDEZ, AGUSTINO; BARISON, MARIA JULIA; SAUTER, ISMAEL PRETTO; PAVANI, RAPHAEL SOUZA; MOURA, ALEXANDRE SANTOS; FURUSHO PRAL, ELIZABETH MIEKO; CORTEZ, MAURO; ELIAS, MARIA CAROLINA; et al. The glutamine synthetase of Trypanosoma cruzi is required for its resistance to ammonium accumulation and evasion of the parasitophorous vacuole during host-cell infection. PLoS Neglected Tropical Diseases, v. 12, n. 1, . (13/07467-1, 16/06034-2, 15/10580-0, 14/10443-0, 16/50050-2)
SERRANO-BUENO, GLORIA; MANUEL MADRONAL, JUAN; MANZANO-LOPEZ, JAVIER; MUNIZ, MANUEL; ROMAN PEREZ-CASTINEIRA, JOSE; HERNANDEZ, AGUSTIN; SERRANO, AURELIO. Nuclear proteasomal degradation of Saccharomyces cerevisiae inorganic pyrophosphatase Ipp1p, a nucleocytoplasmic protein whose stability depends on its subcellular localization. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1866, n. 6, p. 1019-1033, . (14/10443-0)
VERDAGUER, IGNASI BOFILL; CRISPIM, MARCELL; HERNANDEZ, AGUSTIN; KATZIN, ALEJANDRO MIGUEL. The Biomedical Importance of the Missing Pathway for Farnesol and Geranylgeraniol Salvage. Molecules, v. 27, n. 24, p. 15-pg., . (14/10443-0, 19/13419-6, 17/22452-1, 18/02924-9)
PINO, LIDIA; RECUPERO, VINCENZO; HERNANDEZ, AGUSTIN. A Useful Excel-Based Program for Kinetic Model Discrimination. CHEMENGINEERING, v. 2, n. 4, p. 10-pg., . (14/10443-0)
ROXANA GUTIERREZ-ARMIJOS, L.; SUSSMANN, RODRIGO A. C.; SILBER, ARIEL M.; CORTEZ, MAURO; HERNANDEZ, AGUSTIN. Abnormal sterol-induced cell wall glucan deficiency in yeast is due to impaired glucan synthase transport to the plasma membrane. Biochemical Journal, v. 477, n. 24, p. 4729-4744, . (14/10443-0, 16/06034-2, 12/24105-3)
HERNANDEZ, AGUSTIN; HERRERA-PALAU, ROSANA; MADRONAL, JUAN M.; ALBI, TOMAS; LOPEZ-LLUCH, GUILLERMO; PEREZ-CASTINEIRA, JOSE R.; NAVAS, PLACIDO; VALVERDE, FEDERICO; SERRANO, AURELIO. Vacuolar H+-Pyrophosphatase AVP1 is Involved in Amine Fungicide Tolerance in Arabidopsis thaliana and Provides Tridemorph Resistance in Yeast. FRONTIERS IN PLANT SCIENCE, v. 7, . (14/10443-0)

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