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PXD079846-1

PXD079846 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLactate-driven lysine lactylation mediates high-level colistin resistance in Salmonella
DescriptionIntracellular pathogens are particularly refractory to antibiotic eradication, leading to persistent and relapsing infections. However, how intracellular metabolic microenvironments shape antibiotic resistance phenotypes remains poorly understood. Here we delineate a metabolic-regulatory axis wherein Salmonella Typhimurium undergoes profound metabolic rewiring upon intramacrophage adaptation, suppressing oxidative phosphorylation and the tricarboxylic acid (TCA) cycle while upregulating anaerobic glycolysis. This metabolic shift generates elevated lactate levels that drive widespread lysine lactylation, including modifications on the two-component system regulators PmrA and PmrD. Lactylation at specific residues stabilizes phosphorylated PmrA, thereby activating lipopolysaccharide modification genes that remodel the outer membrane charge to confer high-level colistin resistance. Critically, metabolic intervention with exogenous citrate restores TCA cycle activity, reduces lactate production and subsequent PmrA/D lactylation, and resensitizes bacteria to colistin both in vitro and in vivo. These findings reveal metabolic reprogramming as a deterministic driver of post-translational regulatory networks governing antibiotic resistance, offering a paradigm for targeting bacterial metabolism to combat drug-resistant bacteria.
HostingRepositoryiProX
AnnounceDate2026-06-17
AnnouncementXMLSubmission_2026-06-17_20:38:20.043.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterShuang Zhou
SpeciesList scientific name: Salmonella enterica subsp. enterica serovar Typhimurium str. 798; NCBI TaxID: 1008297;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-06-17 20:37:51ID requested
12026-06-17 20:38:20announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Antimicrobial resistance, bacteria, colistin, lysine lactylation, metabolism
Contact List
Yuan Liu
contact affiliationYang Zhou University
contact emailliuyuan2018@yzu.edu.cn
lab head
Shuang Zhou
contact affiliationYang Zhou University
contact emailzshuang202408@163.com
dataset submitter
Full Dataset Link List
iProX dataset URI