Molecular, phenotypic and immune response characterization of clinical isolates of Aspergillus nidulans

• Grant number: 17/19821-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2018
• End date: November 15, 2021
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Rafael Wesley Bastos
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 19/00631-7 - Virulence and immune response characterization of clinical isolates of Aspergillus nidulans in a zebrafish infection model, BE.EP.PD

Abstract

Aspergillus nidulans is a fungus that rarely causes infections in humans, except for patients with Chronic Granulomatous Disease (DGC). DGC is a genetic immunodeficiency caused by problems in the production of the NADH oxidase enzyme by phagocytes, which translates into problems in phagocytosis /destruction of pathogens and a deregulated immune system. Although it causes a serious, often fatal disease in these patients, little is known about the genomic information of disease-causing strains in humans and on the immune response against this pathogen. Therefore, the goal of this project is the phenotypic and genetic characterization of two clinical isolates of A. nidulans, whose genome was sequenced by the research group, and to compare them with a reference strain of this species and one of A. fumigatus, the main agent of invasive aspergilosis (IA). In addition, it is intended to understand the difference in macrophage response with normal and defective NADH oxidase activity against infection by the Aspergillus strains. Finally, when obtaining the phenotypic, genetic and response differences between the strains, the objective is to choose some genes that may be involved in the possible differential response of the macrophages to the different strains. These cells will be molecularly modify (at lest three genes), either silencing or introducing the genes in clinical strains. Altogether, this information may contribute to an improved management of IA in CGD patients by unraveling novel pathways that may be suitable to target with therapies aiming at themodulation ofhost responses and/or fungal mechanisms of adaptation.

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)

BASTOS, RAFAEL WESLEY; VALERO, CLARA; SILVA, LILIAN PEREIRA; SCHOEN, TAYLOR; DROTT, MILTON; BRAUER, VERONICA; SILVA-ROCHA, RAFAEL; LIND, ABIGAIL; STEENWYK, JACOB L.; ROKAS, ANTONIS; et al. Functional Characterization of Clinical Isolates of the Opportunistic Fungal Pathogen Aspergillus nidulans. MSPHERE, v. 5, n. 2, MAR-APR 2020. (19/00631-7, 18/14762-3, 16/07870-9, 17/14159-2, 17/19821-5)

EAGAN, JUSTIN L.; STEFFAN, BREANNE N.; ORTIZ, SEBASTIEN C.; DROTT, MILTON T.; GOLDMAN, GUSTAVO H.; HULL, CHRISTINA M.; KELLER, NANCY P.; BASTOS, RAFAEL W.. Inadvertent Selection of a Pathogenic Fungus Highlights Areas of Concern in Human Clinical Practices. JOURNAL OF FUNGI, v. 8, n. 2, p. 11-pg., 2022-02-01. (16/07870-9, 17/19821-5)

DROTT, M. T.; BASTOS, R. W.; ROKAS, A.; RIES, L. N. A.; GABALDON, T.; GOLDMAN, G. H.; KELLER, N. P.; GRECO, C.. Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates. MSPHERE, v. 5, n. 2, MAR-APR 2020. (17/14159-2, 17/19821-5, 19/00631-7, 16/07870-9)

BASTOS, RAFAEL W.; ROSSATO, LUANA; GOLDMAN, GUSTAVO H.; SANTOS, DANIEL A.. ungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyon. PLOS PATHOGENS, v. 17, n. 12, DEC 2021. (16/07870-9, 18/10962-8, 17/19821-5)

BASTOS, RAFAEL WESLEY; AKIYAMA, DANIEL; DOS REIS, THAILA FERNANDA; COLABARDINI, ANA CRISTINA; LUPERINI, RAFAEL SANCHEZ; DE CASTRO, PATRICIA ALVES; BALDINI, REGINA LUCIA; FILL, TAICIA; GOLDMAN, GUSTAVO H.. Secondary Metabolites Produced during Aspergillus fumigatus and Pseudomonas aeruginosa Biofilm Formation. MBIO, v. 13, n. 4, p. 17-pg., 2022-07-20. (17/07536-4, 21/07038-0, 21/11062-3, 17/19821-5, 16/07870-9, 21/00728-0, 16/12948-7)

LIMA, SORAIA LOPES; ROSSATO, LUANA; DE AZEVEDO MELO, ANALY SALLES. Evaluation of the potential virulence of Candida haemulonii species complex and Candida auris isolates in Caenorhabditis elegans as an in vivo model and correlation to their biofilm production capacity. Microbial Pathogenesis, v. 148, NOV 2020. (17/19095-2, 17/19821-5)