Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence

Aílton Pereira da Costa Filho; Guilherme Thomaz Pereira Brancini; Castro PA de; Clara Valero; Filho JA Ferreira; LP Silva; Marina Campos Rocha; Iran Malavazi; João Guilherme de Moraes Pontes; Taícia Fill; RN Silva; Fausto Almeida; Jacob L. Steenwyk; Antonis Rokas; Reis TF dos; Laure N.A. Ries; Gustavo H. Goldman

doi:10.1128/mbio.02458-20

Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence

Aílton Pereira da Costa Filho, Guilherme Thomaz Pereira Brancini, Castro PA de, Clara Valero, Filho JA Ferreira, LP Silva, Marina Campos Rocha, Iran Malavazi, João Guilherme de Moraes Pontes, Taícia Fill, RN Silva, Fausto Almeida, Jacob L. Steenwyk, Antonis Rokas, Reis TF dos, Laure N.A. Ries^*, Gustavo H. Goldman^*

^*Corresponding author for this work

School of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

A. fumigatus is the main etiological agent of invasive pulmonary aspergillosis, a life-threatening fungal disease that occurs in severely immunocompromised humans. Withstanding the host environment is essential for A. fumigatus virulence, and sensing of extracellular cues occurs primarily through G-protein coupled receptors (GPCRs) that activate signal transduction pathways, which, in turn, regulate fungal development, metabolism, virulence, and mycotoxin biosynthesis. The A. fumigatus genome encodes 15 putative classical GPCRs, with only three having been functionally characterized to date. In this work, we show that the two GPCRs GprM and GprJ regulate the phosphorylation of the mitogen-activated protein kinase MpkA and thus control the regulation of the cell wall integrity pathway. GprM and GprJ are also involved in the regulation of the production of the secondary metabolites fumagillin, pyripyropene, fumigaclavine C, fumiquinazoline, melanin, and fumitremorgin, and this regulation partially occurs through the activation of MpkA. Furthermore, GprM and GprJ are important for virulence in the insect model Galleria mellonella . This work therefore functionally characterizes two GPCRs and shows how they regulate several intracellular pathways that have been shown to be crucial for A. fumigatus virulence.

Original language	English
Number of pages	0
Journal	mBio
Volume	11
Issue number	5
DOIs	https://doi.org/10.1128/mbio.02458-20
Publication status	Published - 27 Oct 2020

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Filho, A. P. D. C., Brancini, G. T. P., de, C. PA., Valero, C., Ferreira, F. JA., Silva, LP., Rocha, M. C., Malavazi, I., Pontes, J. G. D. M., Fill, T., Silva, RN., Almeida, F., Steenwyk, J. L., Rokas, A., dos, R. TF., Ries, L. N. A., & Goldman, G. H. (2020). Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence. mBio, 11(5). https://doi.org/10.1128/mbio.02458-20

@article{4401dafdc8f74bb3b1f365049c27272e,

title = "Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence",

abstract = " A. fumigatus is the main etiological agent of invasive pulmonary aspergillosis, a life-threatening fungal disease that occurs in severely immunocompromised humans. Withstanding the host environment is essential for A. fumigatus virulence, and sensing of extracellular cues occurs primarily through G-protein coupled receptors (GPCRs) that activate signal transduction pathways, which, in turn, regulate fungal development, metabolism, virulence, and mycotoxin biosynthesis. The A. fumigatus genome encodes 15 putative classical GPCRs, with only three having been functionally characterized to date. In this work, we show that the two GPCRs GprM and GprJ regulate the phosphorylation of the mitogen-activated protein kinase MpkA and thus control the regulation of the cell wall integrity pathway. GprM and GprJ are also involved in the regulation of the production of the secondary metabolites fumagillin, pyripyropene, fumigaclavine C, fumiquinazoline, melanin, and fumitremorgin, and this regulation partially occurs through the activation of MpkA. Furthermore, GprM and GprJ are important for virulence in the insect model Galleria mellonella . This work therefore functionally characterizes two GPCRs and shows how they regulate several intracellular pathways that have been shown to be crucial for A. fumigatus virulence. ",

author = "Filho, {A{\'i}lton Pereira da Costa} and Brancini, {Guilherme Thomaz Pereira} and de, {Castro PA} and Clara Valero and Ferreira, {Filho JA} and LP Silva and Rocha, {Marina Campos} and Iran Malavazi and Pontes, {Jo{\~a}o Guilherme de Moraes} and Ta{\'i}cia Fill and RN Silva and Fausto Almeida and Steenwyk, {Jacob L.} and Antonis Rokas and dos, {Reis TF} and Ries, {Laure N.A.} and Goldman, {Gustavo H.}",

year = "2020",

month = oct,

day = "27",

doi = "10.1128/mbio.02458-20",

language = "English",

volume = "11",

journal = "mBio",

issn = "2161-2129",

publisher = "American Society for Microbiology",

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Filho, APDC, Brancini, GTP, de, CPA, Valero, C, Ferreira, FJA, Silva, LP, Rocha, MC, Malavazi, I, Pontes, JGDM, Fill, T, Silva, RN, Almeida, F, Steenwyk, JL, Rokas, A, dos, RTF, Ries, LNA & Goldman, GH 2020, 'Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence', mBio, vol. 11, no. 5. https://doi.org/10.1128/mbio.02458-20

Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence. / Filho, Aílton Pereira da Costa; Brancini, Guilherme Thomaz Pereira; de, Castro PA et al.
In: mBio, Vol. 11, No. 5, 27.10.2020.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence

AU - Filho, Aílton Pereira da Costa

AU - Brancini, Guilherme Thomaz Pereira

AU - de, Castro PA

AU - Valero, Clara

AU - Ferreira, Filho JA

AU - Silva, LP

AU - Rocha, Marina Campos

AU - Malavazi, Iran

AU - Pontes, João Guilherme de Moraes

AU - Fill, Taícia

AU - Silva, RN

AU - Almeida, Fausto

AU - Steenwyk, Jacob L.

AU - Rokas, Antonis

AU - dos, Reis TF

AU - Ries, Laure N.A.

AU - Goldman, Gustavo H.

PY - 2020/10/27

Y1 - 2020/10/27

N2 - A. fumigatus is the main etiological agent of invasive pulmonary aspergillosis, a life-threatening fungal disease that occurs in severely immunocompromised humans. Withstanding the host environment is essential for A. fumigatus virulence, and sensing of extracellular cues occurs primarily through G-protein coupled receptors (GPCRs) that activate signal transduction pathways, which, in turn, regulate fungal development, metabolism, virulence, and mycotoxin biosynthesis. The A. fumigatus genome encodes 15 putative classical GPCRs, with only three having been functionally characterized to date. In this work, we show that the two GPCRs GprM and GprJ regulate the phosphorylation of the mitogen-activated protein kinase MpkA and thus control the regulation of the cell wall integrity pathway. GprM and GprJ are also involved in the regulation of the production of the secondary metabolites fumagillin, pyripyropene, fumigaclavine C, fumiquinazoline, melanin, and fumitremorgin, and this regulation partially occurs through the activation of MpkA. Furthermore, GprM and GprJ are important for virulence in the insect model Galleria mellonella . This work therefore functionally characterizes two GPCRs and shows how they regulate several intracellular pathways that have been shown to be crucial for A. fumigatus virulence.

AB - A. fumigatus is the main etiological agent of invasive pulmonary aspergillosis, a life-threatening fungal disease that occurs in severely immunocompromised humans. Withstanding the host environment is essential for A. fumigatus virulence, and sensing of extracellular cues occurs primarily through G-protein coupled receptors (GPCRs) that activate signal transduction pathways, which, in turn, regulate fungal development, metabolism, virulence, and mycotoxin biosynthesis. The A. fumigatus genome encodes 15 putative classical GPCRs, with only three having been functionally characterized to date. In this work, we show that the two GPCRs GprM and GprJ regulate the phosphorylation of the mitogen-activated protein kinase MpkA and thus control the regulation of the cell wall integrity pathway. GprM and GprJ are also involved in the regulation of the production of the secondary metabolites fumagillin, pyripyropene, fumigaclavine C, fumiquinazoline, melanin, and fumitremorgin, and this regulation partially occurs through the activation of MpkA. Furthermore, GprM and GprJ are important for virulence in the insect model Galleria mellonella . This work therefore functionally characterizes two GPCRs and shows how they regulate several intracellular pathways that have been shown to be crucial for A. fumigatus virulence.

U2 - 10.1128/mbio.02458-20

DO - 10.1128/mbio.02458-20

M3 - Article

SN - 2161-2129

VL - 11

JO - mBio

JF - mBio

IS - 5

ER -

Aspergillus fumigatus G-Protein Coupled Receptors GprM and GprJ Are Important for the Regulation of the Cell Wall Integrity Pathway, Secondary Metabolite Production, and Virulence

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