The protein phosphatase PhzA of A. fumigatus is involved in oxidative stress tolerance and fungal virulence

Muszkieta, Laetitia; Carrion, Steven de Jesus; Robinet, Pauline; Beau, Rémi; Elbim, Carole; Pearlman, Eric; Latgé, Jean Paul

doi:10.1016/j.fgb.2014.02.009

Cited by 22 publications

(17 citation statements)

References 27 publications

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“…In C. albicans , the lack of PPZ1 led to impaired virulence in a mouse model (Ádám et al ., ). In A. fumigatus , deletion of PPZA also showed a defect in virulence in a murine model of corneal infection (Muszkieta et al ., ). However, in this study, ΔFgPPZ1 (ΔFg00852) did not show any detectable defects in virulence.…”

Section: Discussionmentioning

confidence: 98%

Functional analysis of the Fusarium graminearum phosphatome

et al. 2015

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Summary Phosphatases are known to play important roles in the regulation of various cellular processes in eukaryotes. However, systematic characterization of the phosphatome has not been reported in phytopathogenic fungi. The wheat scab fungus Fusarium graminearum contains 82 putative phosphatases. The biological functions of each phosphatase were investigated in this study. Although 11 phosphatase genes appeared to be essential, deletion mutants of the other 71 phosphatase genes were obtained and characterized for changes in 15 phenotypes, including vegetative growth, nutrient response and virulence. Overall, the deletion of 63 phosphatase genes resulted in changes in at least one of the phenotypes assayed. Interestingly, the deletion of four genes (Fg06297, Fg03333, Fg03826 and Fg07932) did not dramatically affect hyphal growth, but led to strongly reduced virulence. Western blot analyses showed that three phosphatases (Fg10516, Fg03333 and Fg12867) functioned as negative regulators of the mitogen‐activated protein kinase signaling pathways. In addition, we found, for the first time, that FgCdc14 is dispensable for growth, but plays an important role in ribosome biogenesis. Overall, in this first functional characterization of the fungal phosphatome, phosphatases important for various aspects of hyphal growth, development, plant infection and secondary metabolism were identified in the phytopathogenic fungus F. graminearum.

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Section: Discussionmentioning

confidence: 98%

Functional analysis of the Fusarium graminearum phosphatome

et al. 2015

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“…The calcineurin phosphatase is central to calcium signaling and plays an important role in determining fungal cell morphology and virulence (Steinbach et al, 2007). In human (Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus) and plant pathogens (Fusarium spp., Sclerotinia sclerotiorum, Ustilago maydis, Magnaporthe oryzae and Botrytis cinerea), other protein phosphatases have been described as regulating mating, asexual development, differentiation, cation homeostasis, CWI, oxidative stress, virulence and pathogenicity (Erental et al, 2007;Di Stasio et al, 2009;Feng et al, 2010;Jiang et al, 2011;Adám et al, 2012;Du et al, 2013;Shin et al, 2013;Yang et al, 2013a,b;Lee et al, 2014;Muszkieta et al, 2014;Yu et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

High osmolarity glycerol response PtcB phosphatase is important for Aspergillus fumigatus virulence

Winkelströter

Bom

Castro

et al. 2015

Molecular Microbiology

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SummaryAspergillus fumigatus is a fungal pathogen that is capable of adapting to different host niches and to avoid host defenses. An enhanced understanding of how, and which, A. fumigatus signal transduction pathways are engaged in the regulation of these processes is essential for the development of improved disease control strategies. Protein phosphatases are central to numerous signal transduction pathways. To comprehend the functions of protein phosphatases in A. fumigatus, 32 phosphatase catalytic subunit encoding genes were identified. We have recognized PtcB as one of the phosphatases involved in the high osmolarity glycerol response (HOG) pathway. The ΔptcB mutant has both increased phosphorylation of the p38 MAPK (SakA) and expression of osmo-dependent genes. The ΔptcB strain was more sensitive to cell wall damaging agents, had increased chitin and β-1,3-glucan, and impaired biofilm formation. The ΔptcB strain was avirulent in a murine model of invasive pulmonary aspergillosis. These results stress the importance of the HOG pathway in the regulation of pathogenicity determinants and virulence in A. fumigatus.

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“…In this work, we demonstrated that the PpzA was important for A. fumigatus virulence in a low-dose murine infection model. Similarly, a previous study reported that the ppzA mutant showed a defect in virulence in an experimental model of corneal infection in immunocompetent animals (Muszkieta et al, 2014). In Candida albicans, the lack of PPZ1 causes impaired virulence in a mouse virulence model (Adám et al, 2012).…”

Section: Analysis Of Chromosomal Patterns Of Gene Expression Inmentioning

confidence: 77%

“…fumigatus protein phosphatase null mutants that are associated to iron assimilation because they have reduced growth during iron starvation (Winkelströter et al, ). Among these protein phosphatases, we have identified the gene ppzA that codes for the catalytic subunit of PPZ and it was previously shown to be involved in oxidative stress tolerance (Leiter et al, ; Muszkieta et al, ). Here, we investigated the role played by PpzA during iron assimilation by using a combined transcriptomic and proteomic analysis comparing the corresponding wild‐type strain with ∆ ppzA mutant under iron starvation conditions.…”

Section: Discussionmentioning

confidence: 99%

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Aspergillus fumigatusprotein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence

Manfiolli

Castro

Reis

et al. 2017

Cellular Microbiology

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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.

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The protein phosphatase PhzA of A. fumigatus is involved in oxidative stress tolerance and fungal virulence

Cited by 22 publications

References 27 publications

Functional analysis of the Fusarium graminearum phosphatome

Functional analysis of the Fusarium graminearum phosphatome

High osmolarity glycerol response PtcB phosphatase is important for Aspergillus fumigatus virulence

Aspergillus fumigatusprotein phosphatase PpzA is involved in iron assimilation, secondary metabolite production, and virulence

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