PXD056622

PXD056622 is an original dataset announced via ProteomeXchange.

Title	Eating the brain - a multidisciplinary study provides new insights into the mechanisms underlying the cytopathogenicity of Naegleria fowleri.
Description	Naegleria fowleri, the causative agent of primary amoebic meningoencephalitis (PAM), requires increased research attention due to its high lethality and the potential for increased incidence as a result of global warming. The aim of this study was to investigate the interactions between N. fowleri and host cells in order to elucidate the mechanisms underlying the pathogenicity of this amoeba. A co-culture system comprising human fibrosarcoma cells was established to study both contact-dependent and contact-independent cytopathogenicity. Proteomic analyses of the amoebas exposed to human cell cultures or passaged through mouse brain were used to identify novel virulence factors. Our results indicate that actin dynamics, regulated by Arp2/3 and Src kinase, play a considerable role in amoeba cell ingestion. We have identified three promising candidate virulence factors, namely lysozyme, cystatin and hemerythrin, which may be critical in facilitating N. fowleri evasion of host defenses, migration to the brain and induction of a lethal infection. Long-term co-culture secretome analysis revealed an increase in protease secretion, which enhances N. fowleri cytopathogenicity. Raman microspectroscopy revealed significant metabolic differences between axenic and brain-isolated amoebae, particularly in lipid storage and utilization. Taken together, our findings provide important new insights into the pathogenic mechanisms of N. fowleri and highlight potential targets for therapeutic intervention against PAM.
HostingRepository	PRIDE
AnnounceDate	2025-02-24
AnnouncementXML	Submission_2025-02-24_08:12:32.385.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pavel Talacko
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Naegleria fowleri; NCBI TaxID: 5763; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Klebsiella aerogenes; NCBI TaxID: 548;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-08 09:16:46	ID requested
⏵ 1	2025-02-24 08:12:32	announced

10.1371/JOURNAL.PPAT.1012995;

submitter keyword: virulence, hemerythrin,Naegleria fowleri, lysozym, cystatin, secretome

Robert Sutak
contact affiliation	Department of Parasitology, Faculty of Science, Charles University, BIOCEV, Vestec, Czech Republic
contact email	sutak@natur.cuni.cz
lab head
Pavel Talacko
contact affiliation	BIOCEV, Faculty of Science, Charles University in Prague
contact email	pavel.talacko@natur.cuni.cz
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/02/PXD056622

PRIDE project URI

• PRIDE
  1. PXD056622
     1. Label: PRIDE project
     2. Name: Eating the brain - a multidisciplinary study provides new insights into the mechanisms underlying the cytopathogenicity of Naegleria fowleri.