PXD075873-1

PXD075873 is an original dataset announced via ProteomeXchange.

Title	Beyond Inhibition - Sub-lethal Rifampicin-induced molecular adaptations confer phenotypic drug tolerance in Mycobacteria
Description	This study investigates how sub-lethal concentrations of rifampicin act as a signalling stimulus that induces phenotypic drug tolerance in mycobacteria. Using Mycobacterium smegmatis as a fast-growing model and validating findings in the attenuated Mycobacterium tuberculosis H37Ra strain, we examined growth dynamics and proteomic adaptations following exposure to half the minimum inhibitory concentration (MIC) of rifampicin. Growth assays demonstrated a transient growth deceleration followed by recovery, indicative of acquired phenotypic tolerance. Deep data-independent acquisition parallel accumulation–serial fragmentation (DIA-PASEF) proteomics was employed to capture early (45 min) and adaptive (180 min) molecular responses in M. smegmatis, with early validation in M. tuberculosis H37Ra. Proteomic analyses revealed rapid and dynamic remodelling of transcriptional, translational, metabolic, and stress-response pathways, including ribosomal perturbation, altered purine biosynthesis, activation of resistance-associated regulators, and modulation of predicted rifampicin influx and efflux systems. In M. tuberculosis H37Ra, conserved responses were accompanied by pronounced cell envelope remodelling via polyketide synthase pathways. Functional validation confirmed that sub-MIC rifampicin pre-exposure primes mycobacteria for enhanced tolerance to lethal drug concentrations. These findings highlight sub-lethal antibiotic exposure as a critical driver of phenotypic tolerance, with important implications for tuberculosis treatment efficacy and resistance evolution.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-08_01:27:17.048.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Blake Stuart
SpeciesList	scientific name: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155); NCBI TaxID: NEWT:246196; scientific name: Mycobacterium tuberculosis H37Ra; NCBI TaxID: NEWT:419947;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-19 12:39:12	ID requested
⏵ 1	2026-06-08 01:27:17	announced

10.1021/acsinfecdis.5c00701;

Stuart BD, van der Merwe A, Chengalroyen MD, Moosa A, Warner DF, Blackburn JM, Ganief TA, Beyond Inhibition: Sublethal Rifampicin-Induced Molecular Adaptations Confer Phenotypic Drug Tolerance in Mycobacteria. ACS Infect Dis, 12(5):1600-1610(2026) [pubmed]

submitter keyword: None

Tariq Ganief
contact affiliation	Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa, 7925
contact email	tariq.ganief@uct.ac.za
lab head
Blake Stuart
contact affiliation	University of Cape Town
contact email	strbla002@myuct.ac.za
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/PXD075873

PRIDE project URI

• PRIDE
  1. PXD075873
     1. Label: PRIDE project
     2. Name: Beyond Inhibition - Sub-lethal Rifampicin-induced molecular adaptations confer phenotypic drug tolerance in Mycobacteria