Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease

© 2015, American Society for Microbiology. 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 functio...

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Main Authors: Pongpom,M., Liu,H., Xu,W., Snarr,B.D., Sheppard,D.C., Mitchell,A.P., Filler,S.G.
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Published: American Society for Microbiology 2015
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spelling th-cmuir.6653943832-383932015-06-16T07:47:08Z Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease Pongpom,M. Liu,H. Xu,W. Snarr,B.D. Sheppard,D.C. Mitchell,A.P. Filler,S.G. Parasitology Microbiology Immunology Infectious Diseases © 2015, American Society for Microbiology. 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. 2015-06-16T07:47:08Z 2015-06-16T07:47:08Z 2015-01-01 Article 00199567 2-s2.0-84923012197 10.1128/IAI.02685-14 http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84923012197&origin=inward http://cmuir.cmu.ac.th/handle/6653943832/38393 American Society for Microbiology
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Parasitology
Microbiology
Immunology
Infectious Diseases
spellingShingle Parasitology
Microbiology
Immunology
Infectious Diseases
Pongpom,M.
Liu,H.
Xu,W.
Snarr,B.D.
Sheppard,D.C.
Mitchell,A.P.
Filler,S.G.
Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease
description © 2015, American Society for Microbiology. 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.
format Article
author Pongpom,M.
Liu,H.
Xu,W.
Snarr,B.D.
Sheppard,D.C.
Mitchell,A.P.
Filler,S.G.
author_facet Pongpom,M.
Liu,H.
Xu,W.
Snarr,B.D.
Sheppard,D.C.
Mitchell,A.P.
Filler,S.G.
author_sort Pongpom,M.
title Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease
title_short Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease
title_full Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease
title_fullStr Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease
title_full_unstemmed Divergent targets of Aspergillus fumigatus AcuK and AcuM transcription factors during growth in vitro versus invasive disease
title_sort divergent targets of aspergillus fumigatus acuk and acum transcription factors during growth in vitro versus invasive disease
publisher American Society for Microbiology
publishDate 2015
url http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84923012197&origin=inward
http://cmuir.cmu.ac.th/handle/6653943832/38393
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