Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion

Vivien Kurucz, Thomas Krüger, K. Antal, Anna Maria Dietl, Hubertus Haas, I. Pócsi, Olaf Kniemeyer, T. Emri

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the H2O2-induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays. Results: The applied H2O2 treatment, which induced only a negligible stress response in iron-replete cultures, deleteriously affected the fungus under iron deprivation. The majority of stress-induced changes in gene and protein expression was not predictable from data coming from individual stress exposure and was only characteristic for the combination of oxidative stress plus iron deprivation. Our experimental data suggest that the physiological effects of combined stresses and the survival of the fungus highly depend on fragile balances between economization of iron and production of essential iron-containing proteins. One observed strategy was the overproduction of iron-independent antioxidant proteins to combat oxidative stress during iron deprivation, e.g. the upregulation of superoxide dismutase Sod1, the thioredoxin reductase Trr1, and the thioredoxin orthologue Afu5g11320. On the other hand, oxidative stress induction overruled iron deprivation-mediated repression of several genes. In agreement with the gene expression data, growth studies underlined that in A. fumigatus iron deprivation aggravates oxidative stress susceptibility. Conclusions: Our data demonstrate that studying stress responses under separate single stress conditions is not sufficient to understand how A. fumigatus adapts in a complex and hostile habitat like the human body. The combinatorial stress of iron depletion and hydrogen peroxide caused clear non-additive effects upon the stress response of A. fumigatus. Our data further supported the view that the ability of A. fumigatus to cause diseases in humans strongly depends on its fitness attributes and less on specific virulence factors. In summary, A. fumigatus is able to mount and coordinate complex and efficient responses to combined stresses like iron deprivation plus H2O2-induced oxidative stress, which are exploited by immune cells to kill fungal pathogens.

Original languageEnglish
Article number357
JournalBMC Genomics
Volume19
Issue number1
DOIs
Publication statusPublished - May 10 2018

Fingerprint

Aspergillus fumigatus
Oxidative Stress
Iron
Fungi
Human Body
Thioredoxin-Disulfide Reductase
Gene Expression
Thioredoxins
Proteins
Virulence Factors
Growth
Proteomics
Hydrogen Peroxide
Superoxide Dismutase
Ecosystem
Up-Regulation
Antioxidants

Keywords

  • Aspergillus fumigatus
  • Combinatorial stress
  • Iron deprivation
  • Oxidative stress
  • Proteomics
  • Stress response
  • Transcriptomics

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion. / Kurucz, Vivien; Krüger, Thomas; Antal, K.; Dietl, Anna Maria; Haas, Hubertus; Pócsi, I.; Kniemeyer, Olaf; Emri, T.

In: BMC Genomics, Vol. 19, No. 1, 357, 10.05.2018.

Research output: Contribution to journalArticle

Kurucz, Vivien ; Krüger, Thomas ; Antal, K. ; Dietl, Anna Maria ; Haas, Hubertus ; Pócsi, I. ; Kniemeyer, Olaf ; Emri, T. / Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion. In: BMC Genomics. 2018 ; Vol. 19, No. 1.
@article{5c31e4e2510b4122ae35a2559390735c,
title = "Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion",
abstract = "Background: Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the H2O2-induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays. Results: The applied H2O2 treatment, which induced only a negligible stress response in iron-replete cultures, deleteriously affected the fungus under iron deprivation. The majority of stress-induced changes in gene and protein expression was not predictable from data coming from individual stress exposure and was only characteristic for the combination of oxidative stress plus iron deprivation. Our experimental data suggest that the physiological effects of combined stresses and the survival of the fungus highly depend on fragile balances between economization of iron and production of essential iron-containing proteins. One observed strategy was the overproduction of iron-independent antioxidant proteins to combat oxidative stress during iron deprivation, e.g. the upregulation of superoxide dismutase Sod1, the thioredoxin reductase Trr1, and the thioredoxin orthologue Afu5g11320. On the other hand, oxidative stress induction overruled iron deprivation-mediated repression of several genes. In agreement with the gene expression data, growth studies underlined that in A. fumigatus iron deprivation aggravates oxidative stress susceptibility. Conclusions: Our data demonstrate that studying stress responses under separate single stress conditions is not sufficient to understand how A. fumigatus adapts in a complex and hostile habitat like the human body. The combinatorial stress of iron depletion and hydrogen peroxide caused clear non-additive effects upon the stress response of A. fumigatus. Our data further supported the view that the ability of A. fumigatus to cause diseases in humans strongly depends on its fitness attributes and less on specific virulence factors. In summary, A. fumigatus is able to mount and coordinate complex and efficient responses to combined stresses like iron deprivation plus H2O2-induced oxidative stress, which are exploited by immune cells to kill fungal pathogens.",
keywords = "Aspergillus fumigatus, Combinatorial stress, Iron deprivation, Oxidative stress, Proteomics, Stress response, Transcriptomics",
author = "Vivien Kurucz and Thomas Kr{\"u}ger and K. Antal and Dietl, {Anna Maria} and Hubertus Haas and I. P{\'o}csi and Olaf Kniemeyer and T. Emri",
year = "2018",
month = "5",
day = "10",
doi = "10.1186/s12864-018-4730-x",
language = "English",
volume = "19",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion

AU - Kurucz, Vivien

AU - Krüger, Thomas

AU - Antal, K.

AU - Dietl, Anna Maria

AU - Haas, Hubertus

AU - Pócsi, I.

AU - Kniemeyer, Olaf

AU - Emri, T.

PY - 2018/5/10

Y1 - 2018/5/10

N2 - Background: Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the H2O2-induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays. Results: The applied H2O2 treatment, which induced only a negligible stress response in iron-replete cultures, deleteriously affected the fungus under iron deprivation. The majority of stress-induced changes in gene and protein expression was not predictable from data coming from individual stress exposure and was only characteristic for the combination of oxidative stress plus iron deprivation. Our experimental data suggest that the physiological effects of combined stresses and the survival of the fungus highly depend on fragile balances between economization of iron and production of essential iron-containing proteins. One observed strategy was the overproduction of iron-independent antioxidant proteins to combat oxidative stress during iron deprivation, e.g. the upregulation of superoxide dismutase Sod1, the thioredoxin reductase Trr1, and the thioredoxin orthologue Afu5g11320. On the other hand, oxidative stress induction overruled iron deprivation-mediated repression of several genes. In agreement with the gene expression data, growth studies underlined that in A. fumigatus iron deprivation aggravates oxidative stress susceptibility. Conclusions: Our data demonstrate that studying stress responses under separate single stress conditions is not sufficient to understand how A. fumigatus adapts in a complex and hostile habitat like the human body. The combinatorial stress of iron depletion and hydrogen peroxide caused clear non-additive effects upon the stress response of A. fumigatus. Our data further supported the view that the ability of A. fumigatus to cause diseases in humans strongly depends on its fitness attributes and less on specific virulence factors. In summary, A. fumigatus is able to mount and coordinate complex and efficient responses to combined stresses like iron deprivation plus H2O2-induced oxidative stress, which are exploited by immune cells to kill fungal pathogens.

AB - Background: Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the H2O2-induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays. Results: The applied H2O2 treatment, which induced only a negligible stress response in iron-replete cultures, deleteriously affected the fungus under iron deprivation. The majority of stress-induced changes in gene and protein expression was not predictable from data coming from individual stress exposure and was only characteristic for the combination of oxidative stress plus iron deprivation. Our experimental data suggest that the physiological effects of combined stresses and the survival of the fungus highly depend on fragile balances between economization of iron and production of essential iron-containing proteins. One observed strategy was the overproduction of iron-independent antioxidant proteins to combat oxidative stress during iron deprivation, e.g. the upregulation of superoxide dismutase Sod1, the thioredoxin reductase Trr1, and the thioredoxin orthologue Afu5g11320. On the other hand, oxidative stress induction overruled iron deprivation-mediated repression of several genes. In agreement with the gene expression data, growth studies underlined that in A. fumigatus iron deprivation aggravates oxidative stress susceptibility. Conclusions: Our data demonstrate that studying stress responses under separate single stress conditions is not sufficient to understand how A. fumigatus adapts in a complex and hostile habitat like the human body. The combinatorial stress of iron depletion and hydrogen peroxide caused clear non-additive effects upon the stress response of A. fumigatus. Our data further supported the view that the ability of A. fumigatus to cause diseases in humans strongly depends on its fitness attributes and less on specific virulence factors. In summary, A. fumigatus is able to mount and coordinate complex and efficient responses to combined stresses like iron deprivation plus H2O2-induced oxidative stress, which are exploited by immune cells to kill fungal pathogens.

KW - Aspergillus fumigatus

KW - Combinatorial stress

KW - Iron deprivation

KW - Oxidative stress

KW - Proteomics

KW - Stress response

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85046627290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85046627290&partnerID=8YFLogxK

U2 - 10.1186/s12864-018-4730-x

DO - 10.1186/s12864-018-4730-x

M3 - Article

VL - 19

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 357

ER -