PXD042190-1

PXD042190 is an original dataset announced via ProteomeXchange.

Title	Analysis of the Aspergillus fumigatus proteomic response to amphotericin B (AmB) reveals involvement of the Rta1-like protein RtaA in resistance
Description	The filamentous fungus Aspergillus fumigatus is an opportunistic human pathogen, which can cause mycoses and allergies in susceptible individuals. With regard to therapy, the polyene drug amphotericin B (AmB) is still frequently used to treat Aspergillus fumigatus infections due to the fact that it remains effective against azole-resistant Aspergillus strains. AmB binds to ergosterol in the fungal membrane, but its mode of action and the fungal resistance mechanisms involved have not been completely elucidated yet. To get further insights into the drug mechanisms of AmB, we investigated the proteomic profile of A. fumigatus in response to AmB and its liposomal formulation by LC-MS/MS analysis. A significant increase (≥ 2-fold) in abundance of 202 different proteins in response to AmB and 193 in case of liposomal AmB was observed, while the level of 70 and 83 proteins decreased, respectively. In particular, the level of proteins anchored to the membrane, involved in catabolic processes, aromatic acid degradation, or secondary metabolism increased prominently. Of particular note was the more than 300-fold increase of a RTA1 domain-containing protein after AmB treatment. Fungal RTA-like proteins represent lipid-translocating exporters, which are characterized by multiple transmembrane regions and often confer resistance to toxic chemicals. Indeed, the deletion of the corresponding gene in A. fumigatus led to an increased susceptibility to AmB and other antifungal polyenes such as nystatin. Particularly worthy of mention is that some of the most significantly increased proteins included enzymes involved in the biosynthesis of secondary metabolites such as the prenylated polyphenol fumicycline as well as xanthocillin and hexadehydro-astechrome, which both form complexes with transition metals.
HostingRepository	PRIDE
AnnounceDate	2025-01-06
AnnouncementXML	Submission_2025-01-06_05:41:10.299.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Krüger
SpeciesList	scientific name: Neosartorya fumigata (Aspergillus fumigatus); NCBI TaxID: 746128;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-12 08:59:24	ID requested
⏵ 1	2025-01-06 05:41:10	announced

10.1093/FEMSML/UQAE024;

submitter keyword: LC-MS, ergosterol, antifungals,Aspergillus fumigatus, amphotericin B

Axel A. Brakhage
contact affiliation	Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute Jena (Leibniz-HKI), Jena, Germany
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. PXD042190
     1. Label: PRIDE project
     2. Name: Analysis of the Aspergillus fumigatus proteomic response to amphotericin B (AmB) reveals involvement of the Rta1-like protein RtaA in resistance