PXD055475-1

PXD055475 is an original dataset announced via ProteomeXchange.

Title	A dual-mechanism antimicrobial peptide with antimutagenic activity targets the replisome and induces cell envelope stress
Description	To combat the growing threat of multidrug-resistant bacteria, we need to develop novel antibiotics with unique modes of action. This study investigates the antibacterial properties of BTP-001 towards Escherichia coli. BTP-001 is a β-clamp targeting antimicrobial peptide containing an AlkB homologu 2 PCNA-interacting motif (APIM) linked to a cell penetrating peptide composed of 11 arginine residues (R11). Our data indicates that R11 mediates energy-dependent transport of BTP-001 across the cell membrane, possibly via iron transport systems such as the TonB-system. The full-length BTP-001 peptide rapidly affects the bacterial membrane, inducing increased expression and activation of the Cpx, E and Rcs cell envelope stress responses, which trigger the production of reaction oxygen species (ROS). This contributes to a rapid bactericidal effect as evidenced by increased short-term survival by addition of a ROS scavenger. Furthermore, we show that BTP-001 reduces the development of resistance to ciprofloxacin likely by binding to the β-clamp via APIM, thereby inhibiting translesion synthesis. In addition, our multi-omics data suggests that the -clamp is part of ribosomal complexes, and that regulation of translation is targeted by BTP-001. In conclusion, BTP-001 exhibits a multifaceted mode of action which strengthens its potential as a novel therapeutic drug against antibiotic resistant bacteria.
HostingRepository	PRIDE
AnnounceDate	2025-08-24
AnnouncementXML	Submission_2025-08-24_14:12:36.249.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amanda Singleton
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Bacteria; NCBI TaxID: NCBITaxon:2;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-02 08:52:40	ID requested
⏵ 1	2025-08-24 14:12:36	announced

Dataset with its publication pending

submitter keyword: Escherichia coli

Marit Otterlei
contact affiliation	Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), PO Box 8905, N-7491, Trondheim, Norway Phone: +47 72573075,
contact email	marit.otterlei@ntnu.no
lab head
Amanda Singleton
contact affiliation	NTNU
contact email	amanda.singleton@ntnu.no
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055475
     1. Label: PRIDE project
     2. Name: A dual-mechanism antimicrobial peptide with antimutagenic activity targets the replisome and induces cell envelope stress