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烟曲霉中编码蛋白磷酸酶的基因的系统全球分析。

Systematic Global Analysis of Genes Encoding Protein Phosphatases in Aspergillus fumigatus.

作者信息

Winkelströter Lizziane K, Dolan Stephen K, Fernanda Dos Reis Thaila, Bom Vinícius Leite Pedro, Alves de Castro Patrícia, Hagiwara Daisuke, Alowni Raneem, Jones Gary W, Doyle Sean, Brown Neil Andrew, Goldman Gustavo H

机构信息

Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 13083-970 Ribeirão Preto, Brazil.

Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.

出版信息

G3 (Bethesda). 2015 May 5;5(7):1525-39. doi: 10.1534/g3.115.016766.

Abstract

Aspergillus fumigatus is a fungal pathogen that causes several invasive and noninvasive diseases named aspergillosis. This disease is generally regarded as multifactorial, considering that several pathogenicity determinants are present during the establishment of this illness. It is necessary to obtain an increased knowledge of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes. Protein phosphatases are essential to several signal transduction pathways. We identified 32 phosphatase catalytic subunit-encoding genes in A. fumigatus, of which we were able to construct 24 viable deletion mutants. The role of nine phosphatase mutants in the HOG (high osmolarity glycerol response) pathway was evaluated by measuring phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. We were also able to identify 11 phosphatases involved in iron assimilation, six that are related to gliotoxin resistance, and three implicated in gliotoxin production. These results present the creation of a fundamental resource for the study of signaling in A. fumigatus and its implications in the regulation of pathogenicity determinants and virulence in this important pathogen.

摘要

烟曲霉是一种真菌病原体,可引发多种侵袭性和非侵袭性疾病,即曲霉病。鉴于在该疾病发生过程中存在多种致病性决定因素,这种疾病通常被认为是多因素导致的。有必要进一步了解烟曲霉的哪些信号转导途径以及如何参与这些过程的调控。蛋白磷酸酶对多种信号转导途径至关重要。我们在烟曲霉中鉴定出32个编码磷酸酶催化亚基的基因,其中我们能够构建24个可存活的缺失突变体。通过测量p38丝裂原活化蛋白激酶(SakA)的磷酸化和渗透依赖性基因的表达,评估了9个磷酸酶突变体在高渗甘油应答(HOG)途径中的作用。我们还能够鉴定出11种参与铁同化的磷酸酶、6种与抗gliotoxin有关的磷酸酶以及3种与gliotoxin产生有关的磷酸酶。这些结果为研究烟曲霉中的信号传导及其在这种重要病原体中致病性决定因素和毒力调控中的意义创造了一个基础资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e443/4502386/bc74a9bb4c57/1525f1.jpg

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