PXD068720

PXD068720 is an original dataset announced via ProteomeXchange.

Title	Culture filtrate of Mycobacterium tuberculosis clinical isolate S169
Description	Phagosome acidification is one of the challenges faced by Mycobacterium tuberculosis during infection. This intracellular pathogen is known to adapt to its stressful environment though stress response pathways and by secreting proteins to modify the host immune response for survival and proliferation. However, M. tuberculosis also holds the potential to form viable but non-replicating (VBNR) and antibiotic tolerant persisters in response to environmental stress, including acid stress. In this study we used a in vitro acid stress model to stimulate the formation of a VBNR subpopulation in a M. tuberculosis clinical isolate with an increased propensity to form VBNR bacteria. Mass spectrometry-based proteomics was used to characterize the cellular proteome and culture filtrate proteome of actively replicating (pH 6,5) and VBNR enriched (pH 4,5) cultures. We show that in response to acid stress, M. tuberculosis S169 increases the expression of known stress response proteins, including the methyltransferase Rv1405c and the acid stress response two-component regulatory protein TcrX. Interestingly, we found that the dormancy response regulon components were less abundant in acid stressed M. tuberculosis S169. Our protein aggregation capture culture filtrate proteomic approach revealed that the culture filtrates of low pH stressed M. tuberculosis S169 contained less proteins than that of actively replicating cultures. We identified several proteins previously implicated in M. tuberculosis persistence, including toxin-antitoxin proteins (VapC51 and VapB10), the chorismate mutase (Rv1885c), and several uncharacterized proteins. The observed differences identified in the characterisation of this clinical isolate in comparison to published M. tuberculosis H37Rv highlights the need to investigate M. tuberculosis clinical isolates for a more representative understanding of the tuberculosis stress response.
HostingRepository	PRIDE
AnnounceDate	2025-10-04
AnnouncementXML	Submission_2025-10-04_00:05:15.859.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nastassja Kriel
SpeciesList	scientific name: Mycobacterium tuberculosis; NCBI TaxID: NEWT:1773;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-22 23:27:15	ID requested
⏵ 1	2025-10-04 00:05:16	announced

10.1101/2025.10.03.680234;

submitter keyword: acid stress,Tuberculosis, heterogenous, persister, VBNR, TB

Professor Samantha Sampson
contact affiliation	Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town
contact email	ssampson@sun.ac.za
lab head
Nastassja Kriel
contact affiliation	Stellenbosch Univeristy
contact email	nastassja@sun.ac.za
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068720
     1. Label: PRIDE project
     2. Name: Culture filtrate of Mycobacterium tuberculosis clinical isolate S169