PXD052177-1

PXD052177 is an original dataset announced via ProteomeXchange.

Title	Proteomics reveals coordinated stress adaptation by a MazF toxin to conserve carbon, sustain central metabolism, and preserve PDIM biosynthesis in Mycobacterium tuberculosis
Description	In response to host-generated stresses, Mycobacterium tuberculosis (Mtb) reprograms its physiology in myriad ways to establish and maintain an infection, yet the signals that underlie this transformation are not well defined. The abundant toxin-antitoxin (TA) systems harbored in the Mtb genome, including eleven in the mazEF family, are thought to act as stress sensors, yet their roles are largely unknown. Although TA systems from other bacteria are generally thought to impart reversible growth arrest in response to stress, the exquisite specificity of Mtb tRNase toxins instead portends a more nuanced role. Here, we used a proteomics approach to track de novo protein synthesis to uncover molecular events initiated by the Mtb MazF-mt9 toxin (MazF7, Rv2063A). First, we documented striking enrichment of enzymes and transporters derived from the contiguous 36 gene region for phthiocerol dimycocerosate (PDIM) synthesis without an accompanying increase in PDIM lipid production. This paradox was reconciled by concomitant downregulation of proteins comprising the Mce1 transporter (imports host fatty acids), cholesterol breakdown, and β oxidation enzymes (limiting the PDIM precursor methylmalonyl-CoA). Thus, increased catalytic efficiency of the PDIM pathway appears to offset substrate starvation to ensure adequate production of PDIMs essential for Mtb early immune escape and virulence. Finally, isocitrate lyase 1 levels also increased, which in this context are expected to primarily catalyze the glyoxylate shunt to sustain central carbon metabolism while minimizing carbon loss. These exacting proteomic signatures are paralleled within the bedaquiline-treated Mtb transcriptome, highlighting a critical role for MazF-mt9 in orchestrating Mtb stress survival.
HostingRepository	PRIDE
AnnounceDate	2026-03-06
AnnouncementXML	Submission_2026-03-06_09:30:30.279.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bruno Abbadi
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: NEWT:83332;
ModificationList	modified L-alanine residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-10 08:04:16	ID requested
⏵ 1	2026-03-06 09:30:30	announced

10.1128/MSYSTEMS.01814-25;

submitter keyword: None

Nancy Woychik
contact affiliation	Department of Biochemistry and Molecular Biology, Rutgers University, Robert Wood Johnson Medical School, USA
contact email	nancy.woychik@rutgers.edu
lab head
Bruno Abbadi
contact affiliation	Rutgers University
contact email	bla51@rutgers.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052177
     1. Label: PRIDE project
     2. Name: Proteomics reveals coordinated stress adaptation by a MazF toxin to conserve carbon, sustain central metabolism, and preserve PDIM biosynthesis in Mycobacterium tuberculosis