Aspergillusfumigatus protein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence

Author(s):Show less -

Manfiolli, Adriana Oliveira ^[1] ; de Castro, Patricia Alves ^[1] ; dos Reis, Thaila Fernanda ^[1] ; Dolan, Stephen ^[2] ; Doyle, Sean ^[2] ; Jones, Gary ^[2] ; Riano Pachon, Diego M. ^[3] ; Ulas, Mevluet ^[2] ; Noble, Luke M. ^[4] ; Mattern, Derek J. ^{[5, 6]} ; Brakhage, Axel A. ^{[5, 6]} ; Valiante, Vito ^[7] ; Silva-Rocha, Rafael ^[8] ; Bayram, Ozgur ^[2] ; Goldman, Gustavo H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Ribeirao Preto - Brazil

^[2] Maynooth Univ, Dept Biol, Maynooth, Kildare - Ireland

^[3] CNPEM, Lab Nacl Ciencia & Tecnol Bioetanol CTBE, Campinas, SP - Brazil

^[4] NYU, New York, NY - USA

^[5] Univ Jena, Jena - Germany

^[6] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Mol & Appl Microbiol, Jena - Germany

^[7] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Leibniz Res Grp Biobricks Microbial Nat Prod Synt, Jena - Germany

^[8] Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: Cellular Microbiology; v. 19, n. 12 DEC 2017.
• Web of Science Citations: 12

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 ppzA mutant had reduced production of pyripyropene A, fumagillin, fumiquinazoline A, triacetyl-fusarinine C, and helvolic acid. The Delta ppzA 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. (AU)

• FAPESP's process: 14/24951-7 - Identification of targets regulated by Aspergillus fumigatus phosphatase PhzA
• Grantee: Adriana Oliveira Manfiolli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/23942-9 - The function of phosphatase encoding genes in the Aspergillus fumigatus virulence and pathogenicity
• Grantee: Gustavo Henrique Goldman
• Support Opportunities: Research Projects - Thematic Grants