The MpkA MAP kinase module regulates cell wall integrity signaling and pyomelanin formation in Aspergillus fumigatus

Valiante, Vito; Jain, Radhika; Heinekamp, Thorsten; Brakhage, Axel A.

doi:10.1016/j.fgb.2009.08.005

Cited by 134 publications

(171 citation statements)

References 33 publications

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“…The mycelia was frozen and ground in liquid nitrogen. For protein extraction, 0.5 ml lysis buffer 63 containing 10% (v/v) glycerol, 50 mM TrisHCl pH 7.5, 1% (v/v) Triton X-100, 150 mM NaCl, 0.1% (w/v) SDS, 5 mM EDTA, 5 mM sodium orthovanadate, 1 mM PMSF, and 1X Complete Mini-protease inhibitor (Roche Applied Science) was added to the ground mycelium. Extracts were centrifuged at 20,000 g for 40 minutes at 4 C. The supernatants were collected and the protein concentrations were determined using the Bradford method 64 (BioRad).…”

Section: Immunoblot Analysismentioning

confidence: 99%

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

et al. 2016

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Aspergillus fumigatus is an opportunistic fungal pathogen and the most important species causing pulmonary fungal infections. The signaling by calcium is very important for A. fumigatus pathogenicity and it is regulated by the transcription factor CrzA. We have previously used used ChIP-seq (Chromatin Immunoprecipitation DNA sequencing) aiming to identify gene targets regulated by CrzA. We have identified among several genes regulated by calcium stress, the putative flavin transporter, flcA. This transporter belongs to a small protein family composed of FlcA, B, and C. The DflcA null mutant showed several phenotypes, such as morphological defects, increased sensitivity to calcium chelating-agent ethylene glycol tetraacetic acid (EGTA), cell wall or oxidative damaging agents and metals, representative of deficiencies in calcium signaling and iron homeostasis. Increasing calcium concentrations improved significantly the DflcA growth and conidiation, indicating that DflcA mutant has calcium insufficiency. Finally, DflcA-C mutants showed reduced flavin adenine dinucleotide (FAD) and were avirulent in a low dose murine infection model.

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Section: Immunoblot Analysismentioning

confidence: 99%

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

et al. 2016

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“…At least four groups of molecules and genes of A. fumigatus associated with its virulence have been studied intensively (2,54), including cell wall components required for massive growth during infection (46), such as beta-1,3-glucan and galactomannan (AFMP1 and AFMP2) (70); stress response genes and molecules which have been implicated in the evasion from the host immune response, such as cyclic AMP (cAMP)-dependent protein kinases (pkaR and pkaC) (54) and mitogen-activated protein (MAP) kinases (mpkA) (67); a number of genes and molecules which allow A. fumigatus to compete in its environmental niche, such as genes involved in iron (9) and phosphorous acquisition (10,50); and toxins and allergens, as well as enzymatic proteins secreted by A. fumigatus, such as alkaline serine proteases (Alp and Alp2) (53) and phospholipases (59) that damage host cells and facilitate tissue infection. Phospholipases hydrolyze ester linkages in glycerophospholipids, which are one of the major chemical constituents of the host cell envelope and, hence, may destabilize the host cell membrane to mediate microbe entry into host cells and tissues.…”

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confidence: 99%

Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus

Gao

Han

et al. 2012

Infect Immun

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Aspergillus fumigatus is the most prevalent airborne fungal pathogen that induces serious infections in immunocompromised patients. Phospholipases are key enzymes in pathogenic fungi that cleave host phospholipids, resulting in membrane destabilization and host cell penetration. However, knowledge of the impact of phospholipases on A. fumigatus virulence is rather limited. In this study, disruption of the pld gene encoding phospholipase D (PLD), an important member of the phospholipase protein family in A. fumigatus, was confirmed to significantly decrease both intracellular and extracellular PLD activity of A. fumigatus. The pld gene disruption did not alter conidial morphological characteristics, germination, growth, and biofilm formation but significantly suppressed the internalization of A. fumigatus into A549 epithelial cells without affecting conidial adhesion to epithelial cells. Importantly, the suppressed internalization was fully rescued in the presence of 100 M phosphatidic acid, the PLD product. Indeed, complementation of pld restored the PLD activity and internalization capacity of A. fumigatus. Phagocytosis of A. fumigatus conidia by J774 macrophages was not affected by the absence of the pld gene. Pretreatment of conidia with 1-butanol and a specific PLD inhibitor decreased the internalization of A. fumigatus into A549 epithelial cells but had no effect on phagocytosis by J774 macrophages. Finally, loss of the pld gene attenuated the virulence of A. fumigatus in mice immunosuppressed with hydrocortisone acetate but not with cyclophosphamide. These data suggest that PLD of A. fumigatus regulates its internalization into lung epithelial cells and may represent an important virulence factor for A. fumigatus infection.

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“…When the fungal cell wall is exposed to the stress, there is an increase in the transcription of the tyrosine degradation gene cluster (54). This increase, in turn, influences the pyomelanin formation via the MpkA mediated cell wall integrity pathway (55). Moreover, several genes (hppD, hmgX, hmgA and fahA) of the tyrosine degradation cluster were found to be differentially regulated when A. fumigatus was exposed to the immune cells of the host.…”

Section: Pyomelaninmentioning

confidence: 99%

Molecular Insights into Pathogenesis and Infection with Aspergillus fumigatus

Ghazaei¹

2017

MJMS

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The virulence of fungi is dependent on multiple factors, including the immune status of patients and biological features of fungi. In particular, the virulence of Aspergillus fumigatus is due to the complex interaction among various molecules involved in thermotolerance (such as ribosomal biogenesis proteins, α-mannosyltransferase and heat shock proteins), pigment production (DHN-melanin), immune evasion (like melanin and hydrophobin) and nutrient uptake (such as siderophores and zinc transporters). Other molecules also play important roles in the virulence of A. fumigatus, including cell wall components and those which maintain its integrity (for instance β-1-3 glucan, α-1-3 glucan, chitin, galactomannan and mannoproteins) and adhesion (such as hydrophobins), as well as various hydrolytic enzymes (such as serine and aspartic protease, phospholipases, metalloproteinase and dipeptidyl peptidases). Signalling molecules (including G-protein, cAMP, Ras protein and calcineurin) also increase the virulence through altering the metabolic response to stress conditions and toxins (such as gliotoxin, fumitremorgins, fumagatin and helvolic acid).

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The MpkA MAP kinase module regulates cell wall integrity signaling and pyomelanin formation in Aspergillus fumigatus

Cited by 134 publications

References 33 publications

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

The putative flavin carrier family FlcA-C is important forAspergillus fumigatusvirulence

Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus

Molecular Insights into Pathogenesis and Infection with Aspergillus fumigatus

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