Manfiolli, Adriana Oliveira and Alves de Castro, Patricia and Fernanda dos Reis, Thaila and Dolan, Stephen K. and Doyle, John and Jones, Gary W. and Riano-Pachon, Diego Mauricio and Ulas, Mevlut and Noble, Luke M. and Mattern, Derek J. and Brakhage, Axel A. and Valiante, Vito and Silva-Rocha, Rafael and Bayram, Ozgur and Goldman, Gustavo H. (2017) Aspergillus fumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence. Cellular Microbiology, 19 (e12770). ISSN 1462-5822

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Abstract

Metal restriction imposed by mammalian hosts during an infection is a common mechanism of defence to reduce or avoid the pathogen infection. Metals are essential for organism survival due to its involvement in several biological processes. Aspergillus fumigatus causes invasive aspergillosis, a disease that typically manifests in immunocompromised patients. A. fumigatus PpzA, the catalytic subunit of protein phosphatase Z (PPZ), has been recently identified as associated with iron assimilation. A. fumigatus has 2 high‐affinity mechanisms of iron acquisition during infection: reductive iron assimilation and siderophore‐mediated iron uptake. It has been shown that siderophore production is important for A. fumigatus virulence, differently to the reductive iron uptake system. Transcriptomic and proteomic comparisons between ∆ppzA and wild‐type strains under iron starvation showed that PpzA has a broad influence on genes involved in secondary metabolism. Liquid chromatography‐mass spectrometry under standard and iron starvation conditions confirmed that the ΔppzA mutant had reduced production of pyripyropene A, fumagillin, fumiquinazoline A, triacetyl‐fusarinine C, and helvolic acid. The ΔppzA was shown to be avirulent in a neutropenic murine model of invasive pulmonary aspergillosis. PpzA plays an important role at the interface between iron starvation, regulation of SM production, and pathogenicity in A. fumigatus.

Item Type:	Article
Keywords:	Aspergillus fumigatus protein phosphatase PpzA; iron assimilation; secondary metabolite production; virulence;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	11002
Identification Number:	https://doi.org/10.1111/cmi.12770
Depositing User:	Ozgur Bayram
Date Deposited:	02 Sep 2019 14:14
Journal or Publication Title:	Cellular Microbiology
Publisher:	Wiley
Refereed:	Yes
URI:	https://onlinelibrary.wiley.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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