PXD078436

PXD078436 is an original dataset announced via ProteomeXchange.

Title	Tail-specific protease (Tsp) - mediated envelope remodeling and beta-lactam tolerance in Escherichia coli
Description	Bacterial persisters are transiently drug-tolerant cells that survive antibiotic treatment without genetic resistance. While certain cytosolic proteases are known to regulate persistence through toxin-antitoxin and stress pathways, the role of envelope-associated proteolysis remains poorly understood. Here, our high-throughput promoter-reporter screen identified several candidate proteases and subsequent antibiotic treatment of knockout strains lacking these degradative genes revealed that Tsp plays a critical role in beta-lactam persistence. Deletion of tsp markedly reduced cell survival to multiple cell-wall-targeting antibiotics. This loss of tsp also compromised cell envelope integrity and caused the accumulation of periplasmic, membrane-associated, and cell-wall-related proteins, including the DD-endopeptidase MepS, as shown by quantitative proteomics. Comprehensive genetic deletion and overexpression analyses revealed that both loss and excessive activity of envelope-associated proteins, particularly MepS, compromise persistence. Moreover, cell envelope permeabilization and antibiotic sensitivity can be independent, as certain envelope perturbations increased permeability without reducing beta-lactam survival. Altogether, our findings support a model in which Tsp-mediated proteolysis helps prevent aberrant accumulation of peptidoglycan-remodeling proteins that would otherwise destabilize the envelope.
HostingRepository	PRIDE
AnnounceDate	2026-06-18
AnnouncementXML	Submission_2026-06-18_08:43:42.084.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jenet Narzary
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: NEWT:562;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-16 15:18:36	ID requested
⏵ 1	2026-06-18 08:43:42	announced

10.1128/SPECTRUM.00277-26;

submitter keyword: Cell envelope-associated proteins, Escherichia coli, Beta-lactam antibiotics,Bacterial persisters, Tsp protease

Mehmet Orman
contact affiliation	Department of Biomedical Engineering, University of Wisconsin-Madison
contact email	maorman@wisc.edu
lab head
Jenet Narzary
contact affiliation	University of Wisconsin-Madison
contact email	narzary@wisc.edu
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/2026/06/PXD078436

PRIDE project URI

• PRIDE
  1. PXD078436
     1. Label: PRIDE project
     2. Name: Tail-specific protease (Tsp) - mediated envelope remodeling and beta-lactam tolerance in Escherichia coli