PXD030308

PXD030308 is an original dataset announced via ProteomeXchange.

Title	PfAP2-MRP DNA-binding protein is a master regulator of parasite pathogenesis during malaria parasite blood stages
Description	The pathogenicity of the malaria parasites results from their ability to invade and remodel red blood cells (RBCs), expressing antigenic variant proteins for immune evasion and survival, and then to egress from the host cell. These sequential processes require concerted actions of a large number of proteins during the intraerythrocytic developmental cycle (IDC)(Boddey and Cowman, 2013; Cowman et al., 2017; Tan and Blackman, 2021), but the molecular basis of the required regulation is only partially understood. Here, we have characterized an essential Apicomplexan AP2 (ApiAP2) transcription factor (we refer to it as PfAP2-MRP; Master Regulator of Pathogenesis) that shows two peaks of expression during the IDC at 16- and 40-hour post-invasion (h.p.i.). When expression of PfAP2-MRP at 40 h.p.i. was disrupted using an inducible gene knockout approach, ∆PfAP2-MRP parasites unable to form mature merozoites and egress from the host RBCs owing to strong down-regulation of several known egress- and invasion-associated genes, in addition to several novel hypothetical genes thought to be involved in these key life cycle processes. Disruption of PfAP2-MRP expression at 16 h.p.i. results in transcriptional activation of the majority of silenced var genes observed at both bulk and single-cell level. This is also reflected by a significantly higher level of immuno-recognition of the exported proteins on the ∆PfAP2-MRP parasite-infected RBCs by pooled sera from malaria-exposed individuals from an endemic region. In addition, overexpression of many early gametocyte marker genes was also observed in ∆PfAP2-MRP parasites at both 40 h.p.i., and at 16 h.p.i. PfAP2-MRP directly regulates these genes by binding to their promoter region or indirectly through 14 other downstream AP2 transcription factors. Taken together, we conclude that PfAP2-MRP is an upstream transcriptional regulator that participates in mutually exclusive expression patterns shown by the var family of genes and is a critical determinant of parasite's growth during the IDC.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_05:51:59.104.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	AMIT KUMAR SUBUDHI
SpeciesList	scientific name: Plasmodium falciparum; NCBI TaxID: 5833;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-11 15:24:54	ID requested
⏵ 1	2024-01-26 05:52:00	announced

10.1038/s41564-023-01497-6;

Subudhi AK, Green JL, Satyam R, Salunke RP, Lenz T, Shuaib M, Isaioglou I, Abel S, Gupta M, Esau L, Mourier T, Nugmanova R, Mfarrej S, Shivapurkar R, Stead Z, Rached FB, Ostwal Y, Sougrat R, Dada A, Kadamany AF, Fischle W, Merzaban J, Knuepfer E, Ferguson DJP, Gupta I, Le Roch KG, Holder AA, Pain A, DNA-binding protein PfAP2-P regulates parasite pathogenesis during malaria parasite blood stages. Nat Microbiol, 8(11):2154-2169(2023) [pubmed]

submitter keyword: Egress, var,APiap2, P.falciparum, Epigenetics, Invasion

Prof. Arnab Pain
contact affiliation	Microbial Genomic Laboratory Division of Biological and Environmental Sciences and Engineering, Level 4, 4326-WS10, Building 2, King Abdullah University of Science and Technology (KAUST),
contact email	arnab.pain@kaust.edu.sa
lab head
AMIT KUMAR SUBUDHI
contact affiliation	KING ABDULLAH UNIVERSITY OF SCIENCE AND TECHNOLOGY
contact email	amit.subudhi@kaust.edu.sa
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/2024/01/PXD030308

PRIDE project URI

• PRIDE
  1. PXD030308
     1. Label: PRIDE project
     2. Name: PfAP2-MRP DNA-binding protein is a master regulator of parasite pathogenesis during malaria parasite blood stages