PXD075099

PXD075099 is an original dataset announced via ProteomeXchange.

Title	Integrated omics-based mechanistical insights into a membrane-targeting antibacterial
Description	Here, we investigated HSI#6, a small-molecule antibacterial previously identified as a SecA activator, using integrated omics and functional assays. HSI#6 exhibits broad-spectrum bacteriostatic activity and acts through a dual-phase mechanism: transient activation of SecA-dependent secretion followed by membrane perturbation and global stress reprogramming. Time-resolved transcriptomics and proteomics revealed early activation of envelope stress regulons (Cpx, Rcs, Pho), efflux systems, and oxidative stress pathways, followed by suppression of ribosome biogenesis and central metabolism. Comparative analysis and biomarker-based principle component analysis (PCA) positioned HSI#6 within the envelope stress mechanistic space, closely aligned with membrane-active antibiotics yet displaying a distinct signature. Adaptive laboratory evolution (ALE) combined with whole-genome sequencing (WGS) revealed compensatory mutations in topoisomerase 1A gene (topA) and transcriptional regulators, without adaptive resistance emerged even under prolonged selection pressure. These findings establish HSI#6 as a mechanistically unique antibacterial targeting membrane homeostasis with low resistance potential.
HostingRepository	PRIDE
AnnounceDate	2026-05-22
AnnouncementXML	Submission_2026-05-22_09:01:54.731.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haitham Abdallah
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	ZenoTOF 7600

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-02 11:39:26	ID requested
⏵ 1	2026-05-22 09:01:55	announced

Dataset with its publication pending

submitter keyword: None

Lily Karamanou
contact affiliation	LAb of molecular bacteriology, Rega Institute, KU Leuven
contact email	lily.karamanou@kuleuven.be
lab head
Haitham Abdallah
contact affiliation	Lab. of Molecular bacteriology, Rega Institute, KU Leuven
contact email	haitham.abdallah@kuleuven.be
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/2026/05/PXD075099

PRIDE project URI

• PRIDE
  1. PXD075099
     1. Label: PRIDE project
     2. Name: Integrated omics-based mechanistical insights into a membrane-targeting antibacterial