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| Status |
Public on Oct 05, 2021 |
| Title |
Pleiotropic Effects of the P5-Type ATPase SpfA on Stress Response Networks Contribute to Virulence in the Pathogenic Mold Aspergillus fumigatus |
| Organism |
Aspergillus fumigatus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Aspergillus fumigatus is a human-pathogenic mold that extracts nutrients from the environment or from host tissues by secreting hydrolytic enzymes. The ability of A. fumigatus to adjust secretion levels in proportion to demand relies on the assistance of the unfolded protein response (UPR), an adaptive stress response pathway that regulates the unique protein-folding environment of the endoplasmic reticulum (ER). The P5-type ATPase Spf1 has recently been implicated in a novel mechanism of ER homeostasis that involves correcting errors in ER-membrane protein targeting. However, the contribution of this protein to the biology of A. fumigatus is unknown. Here, we employed a gene knockout and RNA sequencing strategy to determine the functional role of the A. fumigatus gene coding for the orthologous P5 ATPase SpfA. The data reveal that the spfA gene is induced by ER stress in a UPR-dependent manner. In the absence of spfA, the A. fumigatus transcriptome shifts toward a profile of altered redox and lipid balance, in addition to a signature of ER stress that includes srcA, encoding a second P-type ATPase in the ER. A DspfA deletion mutant showed increased sensitivity to ER stress, oxidative stress, and antifungal drugs that target the cell wall or plasma membrane. The combined loss of spfA and srcA exacerbated these phenotypes and attenuated virulence in two animal infection models. These findings demonstrate that the ER-resident ATPases SpfA and SrcA act jointly to support diverse adaptive functions of the ER that are necessary for fitness in the host environment.
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| |
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| Overall design |
∆spfA vs Parental strain
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| Web link |
https://doi.org/10.1128/mBio.02735-21
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| |
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| Contributor(s) |
Guirao-Abad JP, Weichert M, Luengo-Gil G, Sez Wah Wong S, Aimanianda V, Grisham C, Malev N, Reddy S, Woollett L, Askew DS |
| Citation(s) |
34663092 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI123158 |
ER stress and calcium in host adaptation of A. fumigatus |
UNIVERSITY OF CINCINNATI |
DAVID S ASKEW |
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| |
| Submission date |
Jun 30, 2021 |
| Last update date |
Oct 27, 2021 |
| Contact name |
Jose Pedro Guirao Abad |
| Organization name |
University of Cincinnati
|
| Department |
Pathology and Laboratory Medicine
|
| Lab |
1152
|
| Street address |
231 Albert Sabin Way
|
| City |
CINCINNATI |
| State/province |
OH |
| ZIP/Postal code |
45267-0529 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL30331 |
NextSeq 550 (Aspergillus fumigatus) |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA742560 |
| SRA |
SRP326241 |
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