PXD032276

PXD032276 is an original dataset announced via ProteomeXchange.

Title	Red blood cell BCL-xL is required for Plasmodium falciparum survival: insights into host-directed malaria therapies
Description	The development of antimalarial drug resistance is an ongoing problem threatening progress towards malaria elimination, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the devel-opment of new antimalarials with untapped targets and low propensity for resistance. In addi-tion, drug repurposing in the context of HDT can lead to a substantial decrease in the time and resources required to develop novel antimalarials. Host BCL-XL is a major target in anti-cancer therapy and is essential for the development of numerous intracellular pathogens. We hypothe-sised that red blood cell BCL-XL is essential for Plasmodium development and tested this hypoth-esis by using six BCL-XL inhibitors, including one FDA-approved compound. All BCL-xL inhibitors tested impaired proliferation of P. falciparum 3D7 parasites in vitro at low parasite inhibitory concentrations. Western blot analysis and immunofluorescence microscopy assays revealed that host BCL-xL is transferred from the host red blood cells (RBCs) to the parasite upon infection. Further, immunoprecipitation of BCL-XL coupled with mass spectrometry analysis identified that BCL-XL forms unique molecular complexes with human μ-calpain in uninfected RBCs, and with human SHOC2 in infected RBCs. These results open exciting perspectives for the development of host-directed antimalarial therapies and drug repurposing efforts.
HostingRepository	PRIDE
AnnounceDate	2022-05-19
AnnouncementXML	Submission_2022-05-19_14:35:30.241.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ghizal Siddiqui
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Plasmodium falciparum 365.1; NCBI TaxID: 1245018;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-14 10:01:18	ID requested
⏵ 1	2022-05-19 14:35:31	announced

Boulet C, Siddiqui G, Gaynor TL, Doerig C, Creek DJ, Carvalho TG, Survival: Insights into Host-Directed Malaria Therapies. Microorganisms, 10(4):(2022) [pubmed]

submitter keyword: BCL-XL

malaria

Plasmodium falciparum

host-directed therapy

red blood cells

host-parasite in-teraction

Teresa Carvalho
contact affiliation	La Trobe University, Bundoora, VIC 3086, Australia
contact email	T.Carvalho@latrobe.edu.au
lab head
Ghizal Siddiqui
contact affiliation	Monash University
contact email	ghizal.siddiqui@monash.edu
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/2022/05/PXD032276

PRIDE project URI

• PRIDE
  1. PXD032276
     1. Label: PRIDE project
     2. Name: Red blood cell BCL-xL is required for Plasmodium falciparum survival: insights into host-directed malaria therapies