PXD068455

PXD068455 is an original dataset announced via ProteomeXchange.

Title	Marine-inspired antimicrobial peptides disrupt gene expression on DNA level
Description	Genome mining of Streptomyces sp. H-KF8 combined with sequence engineering yielded two serum-stable, non-cytotoxic, non-lytic antimicrobial peptides, L3 and L3-K. Initial studies in uropathogenic Escherichia coli suggested membrane effects and nucleoid relaxation, prompting a comprehensive investigation of their mode of action. Tandem mass tag (TMT)-based quantitative proteomics revealed extensive proteome remodelling, with 175 and 120 differentially expressed proteins (DEPs) after treatment with L3 and L3-K, respectively. L3 induced predominantly upregulated responses linked to metabolism, RNA processing, transport, and homeostasis, whereas L3-K mainly caused downregulation of proteins involved in metabolism, transport, and cell structure. Both peptides disrupted ABC transporter–mediated nutrient uptake and elicited stress responses, while L3 specifically perturbed the mal regulon, indicative of broader transcriptional dysregulation. Complementary fluorescent dye displacement and in vitro transcription/translation assays demonstrated non-specific DNA binding, stronger for L3 than L3-K, and potent inhibition of transcriptional and translational processes. Strikingly, inhibitory concentrations paralleled their minimum inhibitory concentrations, directly linking DNA binding and interference with central information processing to antimicrobial activity. Taken together, these findings reveal that L3 and L3-K primarily act by targeting DNA and interfering with the transcription–translation machinery. Beyond offering mechanistic insights, this study also underscores their promise as scaffolds for developing next-generation antimicrobial peptides with DNA-binding, non-membrane-lytic activity.
HostingRepository	PRIDE
AnnounceDate	2026-01-23
AnnouncementXML	Submission_2026-01-23_01:48:28.368.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liisa Arike
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-17 06:02:46	ID requested
⏵ 1	2026-01-23 01:48:29	announced

10.1021/acsinfecdis.5c01000;

Beyer LI, Thoma J, Acha Alarcon L, Unksov IN, Karlsson R, Inda-D, í, az JS, Tietze AA, Marine-Inspired Antimicrobial Peptides Disrupt Gene Expression at the DNA Level. ACS Infect Dis, 12(1):447-459(2026) [pubmed]

submitter keyword: Antimicrobial peptides

Global proteomics

TMT

Luisa Beyer
contact affiliation	Department of Chemistry & Molecular Biology, University of Gothenburg, Sweden
contact email	luisa.beyer@gu.se
lab head
Liisa Arike
contact affiliation	PhD
contact email	liisaarike@gmail.com
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/2026/01/PXD068455

PRIDE project URI

• PRIDE
  1. PXD068455
     1. Label: PRIDE project
     2. Name: Marine-inspired antimicrobial peptides disrupt gene expression on DNA level