PXD070366

PXD070366 is an original dataset announced via ProteomeXchange.

Title	NATURAL PRODUCT DERIVED IANTHELLIFORMISAMINES INHIBIT PROTEIN TRANSLATION AND BLOCK BACTERIAL FLAGELLUM ASSEMBLY
Description	Natural products have been a great source for novel drugs especially antibiotics. Given the current antibiotic crisis, revisiting poorly characterized antibacterial natural products may reveal novel modes of action (MoA) as inspiration for drug development. Here, we selected the natural product class of Ianthelliformisamines (Ian) as suitable candidates for MoA studies due to their reported activity against difficult to treat Gram-negative bacteria such as Escherichia coli. In addition, the electrophilic warhead facilitates covalent binding which enhances the residence time on targets and thereby could limit efflux mechanisms. Synthesis of three Ian analogs along with a chemical probe for activity-based protein profiling (ABPP) retained antibacterial effects which were enhanced in the presence of bicarbonate, an abundant ingredient of human serum. Chemical proteomics with the probe unraveled InfA, involved in the initiation of ribosomal protein biosynthesis, as an essential target which was confirmed by translation assays. Intriguingly, a virulence-associated target stood out as an additional hit, FliC, with a crucial role for flagellum assembly. The recombinant protein was probe-labeled and motility assays as well as transmission electron microscopy (TEM) imaging studies demonstrated impaired motility as well as flagellum assembly, respectively. Of note, this dual MoA translated into reduced invasion of pathogenic E. coli into human host cells highlighting a combined antibiotic/anti-virulence strategy as a promising and rather unexploited approach for further therapeutic development.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_16:45:48.560.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Max Bottlinger
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-05 10:12:31	ID requested
⏵ 1	2026-05-24 16:45:49	announced

10.1021/acschembio.5c01018;

Bottlinger M, Morici M, Fajardo-Ruiz E, Gantner I, Brameyer S, Isselstein M, Berger M, Wilson DN, Jung K, Sieber SA, Natural Product-Derived Ianthelliformisamines Inhibit Protein Translation and Block Bacterial Flagellum Assembly. ACS Chem Biol, 21(5):999-1006(2026) [pubmed]

submitter keyword: ABPP,E. coli K12, Orbitrap Eclipse Tribrid instrument

Stephan A. Sieber
contact affiliation	Dr Stephan A. Sieber, TUM Center for Functional Protein Assemblies (CPA), Department of Chemistry and Chair of Organic Chemistry II, Technical University of Munich, Lichtenbergstraße 4, 85748 Garching, Germany.
contact email	Stephan.Sieber@tum.de
lab head
Max Bottlinger
contact affiliation	Center for Functional Protein Assemblies Department of Bioscience, TUM School of Natural Sciences Technische Universität München Ernst-Otto-Fischer-Straße 8, 85748 Garching, Deutschland.
contact email	max.bottlinger@tum.de
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/PXD070366

PRIDE project URI

• PRIDE
  1. PXD070366
     1. Label: PRIDE project
     2. Name: NATURAL PRODUCT DERIVED IANTHELLIFORMISAMINES INHIBIT PROTEIN TRANSLATION AND BLOCK BACTERIAL FLAGELLUM ASSEMBLY