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Molecular Mechanisms Involved in Paradoxal Growth Induced by Caspofungin in Aspergillus fumigatus

Grant number: 17/07536-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): October 01, 2017
Effective date (End): January 31, 2023
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal Investigator:Gustavo Henrique Goldman
Grantee:Ana Cristina Colabardini
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:21/04977-5 - The identification of new pathways and compounds that can enhance caspofungin activity against Aspergillus fumigatus, AP.TEM
Associated scholarship(s):18/14821-0 - Chromatin Immunoprecipitation-DNA sequencing (ChIP-seq) for identification of genes induced during Caspofungin treatment in Aspergillus fumigatus, BE.EP.PD


Invasive aspergillosis infection due to Aspergillus fumigatus specie causes extensive morbidity and mortality, especially among immunosuppressed patients. Caspofungin is a second choice drug to treat aspergilosis, since azole resistant strains have emerged. It belongs to the first class of cell wall-active agents and target the fungal-specific enzyme glucan synthase, which catalyzes the biosynthesis of ²-(1,3)-glucan, a key cell wall polymer. The bottleneck in this treatment is the antifungal paradoxical effect, which has been described as the reversion of growth inhibition at high doses of caspofungin. This effect appears to be a cellular compensatory response to high osmolarity and cell wall integrity pathways, resulting in alteration of cell wall content and structure. However, the impact of the pathways and interactions between all regulatory proteins and transcription factors has not been fully elucidated. In this work we will use effective tools to study, in great detail, the complex cellular actions and protein interactions following caspofungin drug exposure in an effort to optimize the current therapies against invasive aspergillosis.

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Scientific publications (4)
(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)
DE CASTRO, PATRICIA ALVES; COLABARDINI, ANA CRISTINA; MANFIOLLI, ADRIANA OLIVEIRA; CHIARATTO, JESSICA; SILVA, LILIAN PEREIRA; MATTOS, ELICIANE CEVOLANI; PALMISANO, GIUSEPPE; ALMEIDA, FAUSTO; PERSINOTI, GABRIELA FELIX; ANNICK RIES, LAURE NICOLAS; et al. Aspergillus fumigatus calcium-responsive transcription factors regulate cell wall architecture promoting stress tolerance, virulence and caspofungin resistance. PLOS GENETICS, v. 15, n. 12, . (17/07536-4, 16/21392-2, 14/06863-3, 16/12948-7, 16/07870-9, 16/22062-6, 14/04783-2, 17/19288-5)
COLABARDINI, ANA CRISTINA; WANG, FANG; DONG, ZHIQIANG; PARDESHI, LAKHANSING; ROCHA, MARINA CAMPOS; COSTA, JONAS HENRIQUE; DOS REIS, THAILA FERNANDA; BROWN, ALEC; JABER, QAIS Z.; FRIDMAN, MICHA; et al. eterogeneity in the transcriptional response of the human pathogen Aspergillus fumigatus to the antifungal agent caspofungi. Genetics, v. 220, n. 1, . (18/00315-5, 17/07536-4, 17/19694-3, 16/07870-9)
DE CASTRO, PATRICIA ALVES; VALERO, CLARA; CHIARATTO, JESSICA; COLABARDINI, ANA CRISTINA; PARDESHI, LAKHANSING; SILVA, LILIAN PEREIRA; ALMEIDA, FAUSTO; ROCHA, MARINA CAMPOS; SILVA, ROBERTO NASCIMENTO; MALAVAZI, IRAN; et al. Novel Biological Functions of the NsdC Transcription Factor in Aspergillus fumigatus. MBIO, v. 12, n. 1, . (16/07870-9, 18/00715-3, 16/21392-2, 17/07536-4, 16/22062-6, 16/12948-7, 19/10097-8)
RIES, LAURE N. A.; PARDESHI, LAKHANSING; DONG, ZHICLIANG; TAN, KAELING; STEENWYK, JACOB L.; COLABARDINI, ANA CRISTINA; FERREIRA FILHO, JAIRE A.; DE CASTRO, PATRICIA A.; SILVA, LILIAN P.; PREITE, NYCOLAS W.; et al. The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLOS PATHOGENS, v. 16, n. 7, . (17/14159-2, 17/21983-3, 18/25217-6, 17/07536-4, 17/01188-4, 13/50954-0, 14/00789-6, 13/07937-8, 16/07870-9, 19/09278-8, 16/03322-7)

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