PXD056779

PXD056779 is an original dataset announced via ProteomeXchange.

Title	Co-translational protein aggregation and ribosome stalling as a novel broad-spectrum antibacterial mechanism
Description	Drug- resistant bacteria pose are an urgent global threat health threatto global health, necessitatingrequiring the development of antibacterial compounds with a novel mode of action. Protein biosynthesis accounts for up to half of the energy expenditure of bacterial cells and consequently inhibiting the efficiency or fidelity of the bacterial ribosome is a major target of existing antibiotics. Here we describe an alternative mode of action to that affects the same process:; Allowing allowing translation to proceed but causing co-translational aggregation of the nascent chain. We found a peptide that acts via this mechanism and that is bactericidal against a wide range of pathogenic bacteria, including strains for which novel treatments are most urgently needed such as the ESKAPE pathogens, both in planktonic growth and in biofilms. Proteomics, transcriptomics and biochemical analyses of the inclusion bodies that form in bacteria upon peptide treatment reveal ribosomal proteins, as well the mRNAs and their cognate nascent chains of many proteins in amyloid-like structures assembled in polar inclusion bodies, with a bias for membrane proteins with a fold rich in long-range beta-sheet interactions. The bacterial ssrA ribosome rescue pathway is activated, and ribosome hibernation factors become enriched but fails to prevent this does not prevent the incorporation of the incorporation of hundreds of proteins into the inclusion bodies. Mechanistically, our results show that disrupting ribosomal quality controlprotein homeostasis via co-translational aggregation constitutes a potent target mechanism for the development ofdeveloping broad-spectrum antibacterials.
HostingRepository	PRIDE
AnnounceDate	2025-02-11
AnnouncementXML	Submission_2025-02-11_04:25:46.742.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD056779
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sebastien Carpentier
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-14 03:41:03	ID requested
⏵ 1	2025-02-11 04:25:47	announced

10.6019/PXD056779;

10.1038/S41467-025-56873-Z;

submitter keyword: antimicrobial peptide,protein aggregation

Sebastien Carpentier
contact affiliation	SYBIOMA KULeuven Herestraat 49 3000 Leuven
contact email	sebastien.carpentier@kuleuven.be
lab head
Sebastien Carpentier
contact affiliation	KULeuven
contact email	sebastien.carpentier@kuleuven.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056779
     1. Label: PRIDE project
     2. Name: Co-translational protein aggregation and ribosome stalling as a novel broad-spectrum antibacterial mechanism