Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease.
Identifieur interne : 000541 ( Main/Exploration ); précédent : 000540; suivant : 000542Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease.
Auteurs : Monsicha Pongpom [Thaïlande] ; Hong Liu [États-Unis] ; Wenjie Xu [États-Unis] ; Brendan D. Snarr [Canada] ; Donald C. Sheppard [Canada] ; Aaron P. Mitchell [États-Unis] ; Scott G. Filler [États-Unis]Source :
- Infection and immunity [ 1098-5522 ] ; 2015.
Descripteurs français
- KwdFr :
- Analyse de profil d'expression de gènes, Animaux, Aspergillose (anatomopathologie), Aspergillose (immunologie), Aspergillose (microbiologie), Aspergillus fumigatus (croissance et développement), Aspergillus fumigatus (génétique), Aspergillus fumigatus (immunologie), Aspergillus fumigatus (pathogénicité), Cortisone (administration et posologie), Cortisone (analogues et dérivés), Délétion de gène, Facteurs de transcription (génétique), Facteurs de transcription (métabolisme), Fer (métabolisme), Mâle, Néoglucogenèse (génétique), Protéines fongiques (génétique), Protéines fongiques (métabolisme), Régulation de l'expression des gènes fongiques, Sidérophores (métabolisme), Souris, Souris de lignée BALB C, Sujet immunodéprimé, Transcription génétique, Virulence.
- MESH :
- administration et posologie : Cortisone.
- analogues et dérivés : Cortisone.
- anatomopathologie : Aspergillose.
- croissance et développement : Aspergillus fumigatus.
- génétique : Aspergillus fumigatus, Facteurs de transcription, Néoglucogenèse, Protéines fongiques.
- immunologie : Aspergillose, Aspergillus fumigatus.
- microbiologie : Aspergillose.
- métabolisme : Facteurs de transcription, Fer, Protéines fongiques, Sidérophores.
- pathogénicité : Aspergillus fumigatus.
- Analyse de profil d'expression de gènes, Animaux, Délétion de gène, Mâle, Régulation de l'expression des gènes fongiques, Souris, Souris de lignée BALB C, Sujet immunodéprimé, Transcription génétique, Virulence.
English descriptors
- KwdEn :
- Animals, Aspergillosis (immunology), Aspergillosis (microbiology), Aspergillosis (pathology), Aspergillus fumigatus (genetics), Aspergillus fumigatus (growth & development), Aspergillus fumigatus (immunology), Aspergillus fumigatus (pathogenicity), Cortisone (administration & dosage), Cortisone (analogs & derivatives), Fungal Proteins (genetics), Fungal Proteins (metabolism), Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Fungal, Gluconeogenesis (genetics), Immunocompromised Host, Iron (metabolism), Male, Mice, Mice, Inbred BALB C, Siderophores (metabolism), Transcription Factors (genetics), Transcription Factors (metabolism), Transcription, Genetic, Virulence.
- MESH :
- chemical , administration & dosage : Cortisone.
- chemical , analogs & derivatives : Cortisone.
- genetics : Aspergillus fumigatus, Fungal Proteins, Gluconeogenesis, Transcription Factors.
- growth & development : Aspergillus fumigatus.
- immunology : Aspergillosis, Aspergillus fumigatus.
- chemical , metabolism : Fungal Proteins, Iron, Siderophores, Transcription Factors.
- microbiology : Aspergillosis.
- pathogenicity : Aspergillus fumigatus.
- pathology : Aspergillosis.
- Animals, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation, Fungal, Immunocompromised Host, Male, Mice, Mice, Inbred BALB C, Transcription, Genetic, Virulence.
Abstract
In Aspergillus nidulans, the AcuK and AcuM transcription factors form a complex that regulates gluconeogenesis. In Aspergillus fumigatus, AcuM governs gluconeogenesis and iron acquisition in vitro and virulence in immunosuppressed mice. However, the function of AcuK was previously unknown. Through in vitro studies, we found that A. fumigatus ΔacuK single and ΔacuK ΔacuM double mutants had impaired gluconeogenesis and iron acquisition, similar to the ΔacuM mutant. Also, the ΔacuK, ΔacuM, and ΔacuK ΔacuM mutants had similar virulence defects in mice. However, the ΔacuK mutant had a milder defect in extracellular siderophore activity and induction of epithelial cell damage in vitro than did the ΔacuM mutant. Moreover, overexpression of acuM in the ΔacuK mutant altered expression of 3 genes and partially restored growth under iron-limited conditions, suggesting that AcuM can govern some genes independently of AcuK. Although the ΔacuK and ΔacuM mutants had very similar transcriptional profiles in vitro, their transcriptional profiles during murine pulmonary infection differed both from their in vitro profiles and from each other. While AcuK and AcuM governed the expression of only a few iron-responsive genes in vivo, they influenced the expression of other virulence-related genes, such as hexA and dvrA. Therefore, in A. fumigatus, while AcuK and AcuM likely function as part of the same complex, they can also function independently of each other. Furthermore, AcuK and AcuM have different target genes in vivo than in vitro, suggesting that in vivo infection stimulates unique transcriptional regulatory pathways in A. fumigatus.
DOI: 10.1128/IAI.02685-14
PubMed: 25534941
Affiliations:
- Canada, Thaïlande, États-Unis
- Californie, Pennsylvanie, Québec
- Montréal, Pittsburgh
- Université Carnegie-Mellon, Université McGill
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Le document en format XML
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(anatomopathologie)</term><term>Aspergillose (immunologie)</term><term>Aspergillose (microbiologie)</term><term>Aspergillus fumigatus (croissance et développement)</term><term>Aspergillus fumigatus (génétique)</term><term>Aspergillus fumigatus (immunologie)</term><term>Aspergillus fumigatus (pathogénicité)</term><term>Cortisone (administration et posologie)</term><term>Cortisone (analogues et dérivés)</term><term>Délétion de gène</term><term>Facteurs de transcription (génétique)</term><term>Facteurs de transcription (métabolisme)</term><term>Fer (métabolisme)</term><term>Mâle</term><term>Néoglucogenèse (génétique)</term><term>Protéines fongiques (génétique)</term><term>Protéines fongiques (métabolisme)</term><term>Régulation de l'expression des gènes fongiques</term><term>Sidérophores (métabolisme)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Sujet immunodéprimé</term><term>Transcription génétique</term><term>Virulence</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Cortisone</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Cortisone</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Cortisone</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Cortisone</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Aspergillose</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Aspergillus fumigatus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Aspergillus fumigatus</term><term>Fungal Proteins</term><term>Gluconeogenesis</term><term>Transcription Factors</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Aspergillus fumigatus</term></keywords><keywords scheme="MESH" 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fongiques</term><term>Sidérophores</term></keywords><keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Aspergillus fumigatus</term></keywords><keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Aspergillus fumigatus</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Aspergillosis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Gene Deletion</term><term>Gene Expression Profiling</term><term>Gene Expression Regulation, Fungal</term><term>Immunocompromised Host</term><term>Male</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Transcription, Genetic</term><term>Virulence</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Analyse de profil d'expression de gènes</term><term>Animaux</term><term>Délétion de gène</term><term>Mâle</term><term>Régulation de l'expression des gènes fongiques</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Sujet immunodéprimé</term><term>Transcription génétique</term><term>Virulence</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In Aspergillus nidulans, the AcuK and AcuM transcription factors form a complex that regulates gluconeogenesis. In Aspergillus fumigatus, AcuM governs gluconeogenesis and iron acquisition in vitro and virulence in immunosuppressed mice. However, the function of AcuK was previously unknown. Through in vitro studies, we found that A. fumigatus ΔacuK single and ΔacuK ΔacuM double mutants had impaired gluconeogenesis and iron acquisition, similar to the ΔacuM mutant. Also, the ΔacuK, ΔacuM, and ΔacuK ΔacuM mutants had similar virulence defects in mice. However, the ΔacuK mutant had a milder defect in extracellular siderophore activity and induction of epithelial cell damage in vitro than did the ΔacuM mutant. Moreover, overexpression of acuM in the ΔacuK mutant altered expression of 3 genes and partially restored growth under iron-limited conditions, suggesting that AcuM can govern some genes independently of AcuK. Although the ΔacuK and ΔacuM mutants had very similar transcriptional profiles in vitro, their transcriptional profiles during murine pulmonary infection differed both from their in vitro profiles and from each other. While AcuK and AcuM governed the expression of only a few iron-responsive genes in vivo, they influenced the expression of other virulence-related genes, such as hexA and dvrA. Therefore, in A. fumigatus, while AcuK and AcuM likely function as part of the same complex, they can also function independently of each other. Furthermore, AcuK and AcuM have different target genes in vivo than in vitro, suggesting that in vivo infection stimulates unique transcriptional regulatory pathways in A. fumigatus.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Thaïlande</li><li>États-Unis</li></country><region><li>Californie</li><li>Pennsylvanie</li><li>Québec</li></region><settlement><li>Montréal</li><li>Pittsburgh</li></settlement><orgName><li>Université Carnegie-Mellon</li><li>Université McGill</li></orgName></list><tree><country name="Thaïlande"><noRegion><name sortKey="Pongpom, Monsicha" sort="Pongpom, Monsicha" uniqKey="Pongpom M" first="Monsicha" last="Pongpom">Monsicha Pongpom</name></noRegion></country><country name="États-Unis"><region name="Californie"><name sortKey="Liu, Hong" sort="Liu, Hong" uniqKey="Liu H" first="Hong" last="Liu">Hong Liu</name></region><name sortKey="Filler, Scott G" sort="Filler, Scott G" uniqKey="Filler S" first="Scott G" last="Filler">Scott G. Filler</name><name sortKey="Mitchell, Aaron P" sort="Mitchell, Aaron P" uniqKey="Mitchell A" first="Aaron P" last="Mitchell">Aaron P. Mitchell</name><name sortKey="Xu, Wenjie" sort="Xu, Wenjie" uniqKey="Xu W" first="Wenjie" last="Xu">Wenjie Xu</name></country><country name="Canada"><region name="Québec"><name sortKey="Snarr, Brendan D" sort="Snarr, Brendan D" uniqKey="Snarr B" first="Brendan D" last="Snarr">Brendan D. Snarr</name></region><name sortKey="Sheppard, Donald C" sort="Sheppard, Donald C" uniqKey="Sheppard D" first="Donald C" last="Sheppard">Donald C. Sheppard</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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