Identification of targets regulated by Aspergillus fumigatus phosphatase PhzA

• Grant number: 14/24951-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2015
• End date: February 28, 2018
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Adriana Oliveira Manfiolli
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/07870-9 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence, AP.TEM

Abstract

The genus Aspergillus, which includes almost 200 species, has a tremendous impact on public health both beneficially as the workhorse of industrial applications and negatively as plant and human pathogens. The most serious disease caused by A. fumigatus is invasive aspergillosis (IA). IA occurs most commonly when susceptible individuals inhale conidia. These may germinate in the lung resulting in hyphal outgrowth that penetrates epithelial and endothelial barriers. The incidence of invasive infection in immunocompromised individuals is greater than 50% and often the death rate from 50 to 100%. Iron is an essential micronutrient for all eukaryotes, since it participates in a variety of essential biological processes and many studies have shown that iron is essential for growth and virulence of A. fumigatus. However, the bioavailability of this metal is low inside the host. As a consequence, A. fumigatus and other pathogenic micro-organisms have developed high affinity acquisition mechanisms to obtain iron during infection: reductive iron assimilation (RIA) and siderophore-mediated iron acquisition. A collection of A. fumigatus mutants of all genes encoding phosphatases was created and PhzA was identified as an important phosphatase involved in iron metabolism. Preliminary results showed that the mutant ”phzA is avirulent and displays reduced expression levels of genes involved in the biosynthesis of siderophores under conditions of shortage of iron and consequently the production of siderophore TAFC is also reduced. These unpublished data demonstrated the crucial role of phosphatase PhzA in the mechanism of iron acquisition during conditions of penury of this nutrient. Thus, we believe that the characterization of the pathways that are modulated by the phosphatase PhzA in A. fumigatus will provide opportunities for understanding how A. fumigatus regulates the use of iron for the establishment of infection. Furthermore, the identification of ligands and characterization of targets modulated directly or indirectly by this phosphatase will assist in composing a network of biological interactions that will promote the understanding of which are the major events in the signal transduction level that are important for establishment of infection by A. fumigatus.

Scientific publications

(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)

MANFIOLLI, ADRIANA OLIVEIRA; DE CASTRO, PATRICIA ALVES; DOS REIS, THAILA FERNANDA; DOLAN, STEPHEN; DOYLE, SEAN; JONES, GARY; RIANO PACHON, DIEGO M.; ULAS, MEVLUET; NOBLE, LUKE M.; MATTERN, DEREK J.; et al. Aspergillusfumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence. Cellular Microbiology, v. 19, n. 12, DEC 2017. (14/24951-7, 12/23942-9)

MANFIOLLI, ADRIANA OLIVEIRA; SIQUEIRA, FILIPE SILVA; DOS REIS, THAILA FERNANDA; VAN DIJCK, PATRICK; SCHREVENS, SANNE; HOEFGEN, SANDRA; FOEGE, MARTIN; STRASSBURGER, MARIA; DE ASSIS, LEANDRO JOSE; HEINEKAMP, THORSTEN; et al. Mitogen-Activated Protein Kinase Cross-Talk Interaction Modulates the Production of Melanins in Aspergillus fumigatus. MBIO, v. 10, n. 2, MAR-APR 2019. (14/24951-7, 14/00789-6, 16/07870-9)

YSHII, LIDIA M.; MANFIOLLI, ADRIANA O.; DENADAI-SOUZA, ALEXANDRE; KINOSHITA, PAULA F.; GOMES, MARCELO D.; SCAVONE, CRISTOFORO. Tumor necrosis factor receptor-associated factor 6 interaction with alpha-synuclein enhances cell death through the Nuclear Factor-kB pathway. IBRO REPORTS, v. 9, p. 218-223, DEC 2020. (12/07784-4, 11/10303-5, 14/24951-7, 09/12375-3, 18/01308-2, 16/07427-8, 19/10044-1, 18/14289-6, 13/22196-4)