PXD040137

PXD040137 is an original dataset announced via ProteomeXchange.

Title	Succinylation modification provides a new sight in the treatment of immunocompromised populations with drug-resistant Aspergillus fumigatus infection
Description	The invasive infection of Aspergillus fumigatus poses a serious threat to human health worldwide, especially in immunocompromised patients. At present, triazole drugs are the most common antifungal drugs for aspergillosis. However, due to the emergence of drug-resistant strains, the effect of triazole drugs is greatly limited, resulting in the death rate of infection can even be as high as 80%. Succinylation modification, as a new post-translational modification, is receiving more and more attention but its biological function in triazole resistance is still unclear. In this study, we creatively initiated a first screening of lysine succinylation in A.fumigatus. We identified and found that some of the succinylation sites were significantly different among strains with unequal itraconazole (ITR) resistance. Bioinformatics analysis indicated that the succinylated proteins were involved in a wide range of cellular functions with diverse subcellular localizations and cell metabolism is the most prominent. Further antifungal sensitivity test confirmed the synergistic fungicidal effect of dessuccinylase inhibitor nicotinamide (NAM) on ITR resistant A.fumigatus. In vivo experiment, the treatment of NAM alone or combined with ITR both significantly increased the survival of neutropenia mice with A.fumigatus infection. In vitro experiment showed that NAM enhanced the killing effect of Thp-1 macrophages on A.fumigatus conidia. Our results suggest that lysine succinylation may play an indispensable role in the ITR-resistance of A.fumigatus. Dessuccinylase inhibitor NAM alone or combined with ITR exerted a good effect against A.fumigatus infection, which was concerned with its synergistic fungicidal effect as well as enhancing macrophage killing effect. These results provide mechanistic insights for the treatment of ITR-resistant fungi infection.
HostingRepository	iProX
AnnounceDate	2023-02-15
AnnouncementXML	Submission_2023-05-10_00:35:45.750.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaochun Xue
SpeciesList	scientific name: Aspergillus fumigatus; NCBI TaxID: 746128;
ModificationList	succinylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-15 19:01:54	ID requested
1	2023-02-15 19:02:01	announced
⏵ 2	2023-05-10 00:35:46	announced	2023-05-10: Update publication information.

Chen X, Lei W, Meng H, Jiang Y, Zhang S, Chen H, Du M, Xue X, infection. Front Immunol, 14():1161642(2023) [pubmed]

submitter keyword: Aspergillus fumigatus, drug-resistance, Succinylation

Xiaochun Xue
contact affiliation	905th Hospital of PLA Navy
contact email	xxc2021@126.com
lab head
Xiaochun Xue
contact affiliation	905th Hospital of PLA Navy
contact email	xxc2021@126.com
dataset submitter

iProX dataset URI