PXD056876

PXD056876 is an original dataset announced via ProteomeXchange.

Title	The proteomic response of Aspergillus fumigatus wildtype and rtaA knockout strain to Amphotericin B
Description	Amphotericin B (AmB) and AmBisome are vital treatments for invasive fungal infections, particularly invasive aspergillosis caused by Aspergillus fumigatus spores. However, increasing resistance to AmB in clinical isolates of A. fumigatus is a growing concern. Despite this, the mechanisms of AmB resistance in A. fumigatus remain unclear. In this study, we conducted a proteomic analysis of A. fumigatus exposed to sublethal concentrations of AmB and AmBisome, identifying proteins that were strongly induced by these drugs. One of the most upregulated proteins was RtaA, which encodes a member of the RTA-like protein family, that comprises conserved fungal membrane proteins with putative functions as transporters or translocases. We found that deleting rtaA led to increased polyene sensitivity and overexpression to modest resistance and is mainly located in plasma and partially vacuolar membranes. Interestingly, rtaA expression was only induced by exposure to AmB and nystatin, but not by other antifungals such as itraconazole and caspofungin. Deletion of rtaA did not significantly change the ergosterol content of A. fumigatus, but decreased fluorescence intensity of the sterol-binding stain filipin. This suggests that RtaA is involved in sterol and lipid trafficking, possibly by transporting the target ergosterol from or to lipid droplets. These findings reveal a novel polyene resistance mechanism that warrants further investigation to determine its exact mechanism and importance in clinical resistant isolates of A. fumigatus.
HostingRepository	PRIDE
AnnounceDate	2025-05-05
AnnouncementXML	Submission_2025-05-05_06:07:42.350.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Krüger
SpeciesList	scientific name: Aspergillus fumigatus CEA17; NCBI TaxID: 1266464;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-16 18:05:24	ID requested
⏵ 1	2025-05-05 06:07:43	announced

10.1093/femsml/uqae024;

submitter keyword: Aspergillus fumigatus,Amphotericin B, antifungals, RtaA, LC-MS/MS

Axel A. Brakhage
contact affiliation	Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute (Leibniz-HKI) Jena
contact email	axel.brakhage@leibniz-hki.de
lab head
Thomas Krüger
contact affiliation	Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute
contact email	thomas.krueger@leibniz-hki.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056876
     1. Label: PRIDE project
     2. Name: The proteomic response of Aspergillus fumigatus wildtype and rtaA knockout strain to Amphotericin B