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PXD075040-1

PXD075040 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGenetic and pharmacological inactivation of peptidoglycan remodeling increases antibiotic susceptibility of vancomycin-resistant Enterococcus faecium
DescriptionVancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of healthcare-associated infections globally and demands new approaches for treatment. Here we show that genetic and pharmacological inactivation of a highly conserved NlpC/P60 peptidoglycan hydrolase, secreted antigen A (SagA), enhanced vancomycin susceptibility of VREfm ex vivo and in vivo. Notably, genetic deletion of sagA impaired VREfm peptidoglycan remodeling, growth and increased the activity of vancomycin. We then identified first-in-class covalent NlpC/P60 peptidoglycan hydrolase inhibitors and demonstrated that pharmacological inactivation of SagA activity also impaired peptidoglycan remodeling and increased the efficacy of vancomycin in several VREfm clinical isolates. Our study reveals peptidoglycan hydrolases are druggable targets whose inactivation improves the efficacy of vancomycin against VREfm.
HostingRepositoryPRIDE
AnnounceDate2026-04-13
AnnouncementXMLSubmission_2026-04-13_14:45:30.030.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKyong Fam
SpeciesList scientific name: Enterococcus faecium ERV165; NCBI TaxID: NEWT:1134822;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-02-28 00:29:23ID requested
12026-04-13 14:45:31announced
Publication List
10.1101/2025.09.11.675460;
Fam KT, Chodisetti PK, Wang Z, Homer JA, Smedley CJ, Kitamura S, Silva B, Xiong Y, Hansel-Harris A, Holcomb M, Babarinde S, Turner AM, Van Tyne D, Wilson IA, Forli S, Cravatt BF, Park D, Wolan DW, Moses JE, Hang HC, . bioRxiv, ():(2026) [pubmed]
Keyword List
submitter keyword: antibiotic adjuvant, covalent inhibitor, chemoproteomics,vancomycin-resistant Enterococcus faecium, peptidoglycan hydrolase
Contact List
Howard C. Hang
contact affiliationDepartment of Immunology & Microbiology, Scripps Research, USA
contact emailhhang@scripps.edu
lab head
Kyong Fam
contact affiliationScripps Research
contact emailtfam@scripps.edu
dataset submitter
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Dataset FTP location
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