Deletion of core septin gene aspB in Aspergillus fumigatus results in fungicidal activity of caspofungin
7 affiliations
- 1Department of Biological Sciences, Virginia Tech, Blacksburg 24061, Virginia
- 2Center for Emerging, Zoonotic, and Arthropod-borne Pathogens, Virginia Tech, Blacksburg, Virginia 24061
- 3School of Biological Sciences, Southern Illinois University-Carbondale, Carbondale, Illinois 62901
- 4Michael Hooker Metabolomics and Proteomics Core Facility, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill 27599, North Carolina
- 5Microbiology Program, Southern Illinois University-Carbondale, Carbondale, Illinois 62901
- 6Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia 24061
- 7Fralin Life Science Institute, Virginia Tech, Blacksburg, Virginia 24061
Abstract
Septins are a family of GTP-binding proteins found in many eukaryotic lineages. Although highly conserved throughout many eukaryotes, their functions vary across species. In Aspergillus fumigatus, the etiological agent of invasive aspergillosis, septins participate in a variety of processes, including conidiation, septation, and responses to cell wall stress. Previous studies determined that the ΔaspB septin deletion strain had a greater sensitivity to anti-cell wall drugs, especially the echinocandins, yet the mechanisms behind this augmented sensitivity are unknown. We performed cell viability staining of the septin deletion strains after caspofungin exposure and found that the ΔaspA, ΔaspB, and ΔaspC strains had significantly lower cell viability. Concomitant with the reduced viability, these septin deletion strains are more susceptible to caspofungin on solid media. These results indicate that the septin cytoskeleton is important for A. fumigatus survival in the presence of caspofungin. Due to the potential for improved therapeutic outcome, we followed up using a neutropenic murine model of invasive aspergillosis. Animals infected with the ΔaspB strain and treated with caspofungin showed improved survival compared with the animals infected with the ΔakuBKU80 wild-type or complemented strains. Additionally, histological analysis showed reduced fungal burden in the ΔaspB-infected, caspofungin-treated group. To gain insight into how AspB coordinates fungal response to caspofungin, we used proteomics and identified proteins involved in the septin-dependent response to caspofungin, including four candidate interactors involved in cell wall stress response. Deletion of these candidate genes resulted in increased susceptibility to caspofungin and moderately reduced viability post-drug exposure. Taken together, these data suggest that septin AspB contributes to the fungistatic response to caspofungin.
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BibTeX
@article{busch2026deletion,
title = {{Deletion of core septin gene aspB in Aspergillus fumigatus results in fungicidal activity of caspofungin}},
author = {Rebecca Jean Busch and Carson Doty and C. Allie Mills and Flutur Latifi and Laura E. Herring and Vjollca Konjufca and Francisco Carvallo and Tatiana Boluarte and José M Vargas-Muñiz},
journal = {Molecular Biology of the Cell},
year = {2026},
month = oct,
doi = {10.1091/mbc.e26-03-0151},
url = {https://doi.org/10.1091/mbc.e26-03-0151},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Deletion of core septin gene aspB in Aspergillus fumigatus results in fungicidal activity of caspofungin
AU - Rebecca Jean Busch
AU - Carson Doty
AU - C. Allie Mills
AU - Flutur Latifi
AU - Laura E. Herring
AU - Vjollca Konjufca
AU - Francisco Carvallo
AU - Tatiana Boluarte
AU - José M Vargas-Muñiz
PY - 2026
DA - 2026/10/26
JO - Molecular Biology of the Cell
DO - 10.1091/mbc.e26-03-0151
UR - https://doi.org/10.1091/mbc.e26-03-0151
AB - Septins are a family of GTP-binding proteins found in many eukaryotic lineages. Although highly conserved throughout many eukaryotes, their functions vary across species. In Aspergillus fumigatus, the etiological agent of invasive aspergillosis, septins participate in a variety of processes, including conidiation, septation, and responses to cell wall stress. Previous studies determined that the ΔaspB septin deletion strain had a greater sensitivity to anti-cell wall drugs, especially the echinocandins, yet the mechanisms behind this augmented sensitivity are unknown. We performed cell viability staining of the septin deletion strains after caspofungin exposure and found that the ΔaspA, ΔaspB, and ΔaspC strains had significantly lower cell viability. Concomitant with the reduced viability, these septin deletion strains are more susceptible to caspofungin on solid media. These results indicate that the septin cytoskeleton is important for A. fumigatus survival in the presence of caspofungin. Due to the potential for improved therapeutic outcome, we followed up using a neutropenic murine model of invasive aspergillosis. Animals infected with the ΔaspB strain and treated with caspofungin showed improved survival compared with the animals infected with the ΔakuBKU80 wild-type or complemented strains. Additionally, histological analysis showed reduced fungal burden in the ΔaspB-infected, caspofungin-treated group. To gain insight into how AspB coordinates fungal response to caspofungin, we used proteomics and identified proteins involved in the septin-dependent response to caspofungin, including four candidate interactors involved in cell wall stress response. Deletion of these candidate genes resulted in increased susceptibility to caspofungin and moderately reduced viability post-drug exposure. Taken together, these data suggest that septin AspB contributes to the fungistatic response to caspofungin.
SN - 1059-1524
SN - 1939-4586
ER -