PXD062278

PXD062278 is an original dataset announced via ProteomeXchange.

Title	SIRT5: A Newly Identified Key Host Factor in the Pathogenesis of Apicomplexan Parasites
Description	Apicomplexan parasites are widely distributed and pose significant potential threats to both human and animal health. Neospora caninum (N. caninum), the causative agent of neosporosis, represents a significant threat to the global ruminant industry, emphasizing the urgent need for development of novel antiparasitic drugs. Here we conducted a quantitative mass spectrometry-based analysis of succinylation modification of N. caninum-infected bovine macrophages, revealing substantial alterations in lysine succinylation in both host and N. caninum proteins. Notably, N. caninum enhanced succinylation of key enzymes involved in the pyruvate metabolism, glycolysis, and tricarboxylic acid (TCA) cycle, thereby impacting cellular energy metabolism pathways. Targeted metabonomics confirmed that the differential metabolites induced by N. caninum primarily clustered within these energy metabolism pathways. Sirtuin 5 (SIRT5), a desuccinylase that regulates host protein succinylation, was significantly upregulated following N. caninum infection. Furthermore, we observed enhanced survival rates, reduced parasite burden in tissues, along with decreased pathological changes and tissue injury in SIRT5-deficient mice infected with N. caninum or T. gondii. SIRT5 deficiency mitigated N. caninum or T. gondii -induced injury by suppressing inflammatory cytokine storm and restoring oxidative stress balance. Additionally, we found that SIRT5 regulated host protein succinylation, and several inhibitors targeting the process exhibited anti-parasite effects, suggesting potential drug targets for combating N. caninum infection. These findings elucidate a regulatory mechanism linking succinylation and energy metabolism pathways mediated by N. caninum, revealing promising antiparasite drug targets for the treatment of neosporosis.
HostingRepository	iProX
AnnounceDate	2025-03-27
AnnouncementXML	Submission_2025-03-26_19:45:53.185.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhengkai Wei
SpeciesList	scientific name: Bos taurus; NCBI TaxID: 9913; scientific name: Neospora caninum; NCBI TaxID: 29176;
ModificationList	succinylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-26 19:45:36	ID requested
⏵ 1	2025-03-26 19:45:53	announced

Dataset with its publication pending

submitter keyword: Neospora caninum, Toxoplasma gondii, Succinylation, Metabonomics, Sirtuin 5

Zhengkai Wei
contact affiliation	Southwest University
contact email	wei_zhengkai@126.com
lab head
Zhengkai Wei
contact affiliation	Southwest University
contact email	wei_zhengkai@126.com
dataset submitter

iProX dataset URI