Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lungCitation formats

  • External authors:
  • Hong Liu
  • Wenjie Xu
  • Vincent M Bruno
  • Quynh T Phan
  • Norma V Solis
  • Carol A Woolford
  • Rachel L Ehrlich
  • Amol C Shetty
  • Carrie McCraken
  • Jianfeng Lin
  • Aaron P Mitchell
  • Scott G Filler

Standard

Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung. / Liu, Hong; Xu, Wenjie; Bruno, Vincent M; Phan, Quynh T; Solis, Norma V; Woolford, Carol A; Ehrlich, Rachel L; Shetty, Amol C; McCraken, Carrie; Lin, Jianfeng; Bromley, Michael J; Mitchell, Aaron P; Filler, Scott G.

In: PLoS Pathogens, Vol. 17, No. 3, e1009235, 29.03.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Liu, H, Xu, W, Bruno, VM, Phan, QT, Solis, NV, Woolford, CA, Ehrlich, RL, Shetty, AC, McCraken, C, Lin, J, Bromley, MJ, Mitchell, AP & Filler, SG 2021, 'Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung', PLoS Pathogens, vol. 17, no. 3, e1009235. https://doi.org/10.1371/journal.ppat.1009235

APA

Liu, H., Xu, W., Bruno, V. M., Phan, Q. T., Solis, N. V., Woolford, C. A., Ehrlich, R. L., Shetty, A. C., McCraken, C., Lin, J., Bromley, M. J., Mitchell, A. P., & Filler, S. G. (2021). Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung. PLoS Pathogens, 17(3), [e1009235]. https://doi.org/10.1371/journal.ppat.1009235

Vancouver

Liu H, Xu W, Bruno VM, Phan QT, Solis NV, Woolford CA et al. Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung. PLoS Pathogens. 2021 Mar 29;17(3). e1009235. https://doi.org/10.1371/journal.ppat.1009235

Author

Liu, Hong ; Xu, Wenjie ; Bruno, Vincent M ; Phan, Quynh T ; Solis, Norma V ; Woolford, Carol A ; Ehrlich, Rachel L ; Shetty, Amol C ; McCraken, Carrie ; Lin, Jianfeng ; Bromley, Michael J ; Mitchell, Aaron P ; Filler, Scott G. / Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung. In: PLoS Pathogens. 2021 ; Vol. 17, No. 3.

Bibtex

@article{e744a72bdbad491a98c4b1c829e9479d,
title = "Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung",
abstract = "To gain a better understanding of the transcriptional response of Aspergillus fumigatus during invasive pulmonary infection, we used a NanoString nCounter to assess the transcript levels of 467 A. fumigatus genes during growth in the lungs of immunosuppressed mice. These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the A. fumigatus genome. We found that invasive growth in vivo induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This in vivo transcriptional response is largely mimicked by in vitro growth in Aspergillus minimal medium that is deficient in nitrogen, iron, and/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during in vivo growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was rlmA, which is required for the organism to achieve maximal fungal burden in the lung. The other was sltA, which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of laeA. Using deletion and overexpression mutants, we determined that the attenuated virulence of the ΔsltA mutant is due in part to decreased expression aspf1, which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus, in vivo transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.",
author = "Hong Liu and Wenjie Xu and Bruno, {Vincent M} and Phan, {Quynh T} and Solis, {Norma V} and Woolford, {Carol A} and Ehrlich, {Rachel L} and Shetty, {Amol C} and Carrie McCraken and Jianfeng Lin and Bromley, {Michael J} and Mitchell, {Aaron P} and Filler, {Scott G}",
note = "Funding Information: This work was supported by NIH grants R01AI124566 and R01DE026600 to SGF and APM, U19AI110820 to SGF and VMB, and R01AI141360 to VMB. MJB was supported in part by Wellcome Trust grant 208396/Z/17/Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2021",
month = mar,
day = "29",
doi = "10.1371/journal.ppat.1009235",
language = "English",
volume = "17",
journal = "PL o S Pathogens",
issn = "1553-7374",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Determining Aspergillus fumigatus transcription factor expression and function during invasion of the mammalian lung

AU - Liu, Hong

AU - Xu, Wenjie

AU - Bruno, Vincent M

AU - Phan, Quynh T

AU - Solis, Norma V

AU - Woolford, Carol A

AU - Ehrlich, Rachel L

AU - Shetty, Amol C

AU - McCraken, Carrie

AU - Lin, Jianfeng

AU - Bromley, Michael J

AU - Mitchell, Aaron P

AU - Filler, Scott G

N1 - Funding Information: This work was supported by NIH grants R01AI124566 and R01DE026600 to SGF and APM, U19AI110820 to SGF and VMB, and R01AI141360 to VMB. MJB was supported in part by Wellcome Trust grant 208396/Z/17/Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/3/29

Y1 - 2021/3/29

N2 - To gain a better understanding of the transcriptional response of Aspergillus fumigatus during invasive pulmonary infection, we used a NanoString nCounter to assess the transcript levels of 467 A. fumigatus genes during growth in the lungs of immunosuppressed mice. These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the A. fumigatus genome. We found that invasive growth in vivo induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This in vivo transcriptional response is largely mimicked by in vitro growth in Aspergillus minimal medium that is deficient in nitrogen, iron, and/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during in vivo growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was rlmA, which is required for the organism to achieve maximal fungal burden in the lung. The other was sltA, which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of laeA. Using deletion and overexpression mutants, we determined that the attenuated virulence of the ΔsltA mutant is due in part to decreased expression aspf1, which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus, in vivo transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.

AB - To gain a better understanding of the transcriptional response of Aspergillus fumigatus during invasive pulmonary infection, we used a NanoString nCounter to assess the transcript levels of 467 A. fumigatus genes during growth in the lungs of immunosuppressed mice. These genes included ones known to respond to diverse environmental conditions and those encoding most transcription factors in the A. fumigatus genome. We found that invasive growth in vivo induces a unique transcriptional profile as the organism responds to nutrient limitation and attack by host phagocytes. This in vivo transcriptional response is largely mimicked by in vitro growth in Aspergillus minimal medium that is deficient in nitrogen, iron, and/or zinc. From the transcriptional profiling data, we selected 9 transcription factor genes that were either highly expressed or strongly up-regulated during in vivo growth. Deletion mutants were constructed for each of these genes and assessed for virulence in mice. Two transcription factor genes were found to be required for maximal virulence. One was rlmA, which is required for the organism to achieve maximal fungal burden in the lung. The other was sltA, which regulates of the expression of multiple secondary metabolite gene clusters and mycotoxin genes independently of laeA. Using deletion and overexpression mutants, we determined that the attenuated virulence of the ΔsltA mutant is due in part to decreased expression aspf1, which specifies a ribotoxin, but is not mediated by reduced expression of the fumigaclavine gene cluster or the fumagillin-pseruotin supercluster. Thus, in vivo transcriptional profiling focused on transcription factors genes provides a facile approach to identifying novel virulence regulators.

U2 - 10.1371/journal.ppat.1009235

DO - 10.1371/journal.ppat.1009235

M3 - Article

C2 - 33780518

VL - 17

JO - PL o S Pathogens

JF - PL o S Pathogens

SN - 1553-7374

IS - 3

M1 - e1009235

ER -