PXD022969-2

PXD022969 is an original dataset announced via ProteomeXchange.

Title	Mycobacterium tuberculosis H2S functions as a sink to modulate central metabolism, bioenergetics, and drug susceptibility
Description	H2S is a potent gasotransmitter in eukaryotes and bacteria. Host-derived H2S was shown to profoundly alter M. tuberculosis (Mtb) energy metabolism and growth. However, compelling evidence for endogenous production of H2S and its role in Mtb physiology is lacking. We show that multi-drug-resistant and drug-susceptible clinical Mtb strains produce H2S, whereas H2S production in non-pathogenic M. smegmatis is barely detectable. We identified Rv3684 (Cds1) as an H2S-producing enzyme in Mtb and show that cds1 disruption reduces, but does not eliminate H2S production, suggesting the involvement of multiple genes in H2S production. We identified endogenous H2S to be an effector molecule that maintains bioenergetic homeostasis by regulating respiration. Importantly, H2S plays a key role in central metabolism by modulating the balance between oxidative phosphorylation and glycolysis, and functions as a sink to recycle sulfur atoms back to cysteine to maintain sulfur homeostasis. Lastly, Mtb-generated H2S regulates redox homeostasis and susceptibility to the anti-TB drugs clofazimine and rifampicin. These findings reveal previously unknown facets of Mtb physiology and have implications for routine laboratory culturing, understanding drug susceptibility, and improved diagnostics.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:24:32.076.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tafara Kunota
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv_2009; NCBI TaxID: 747078;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-07 03:55:19	ID requested
1	2021-08-16 00:13:09	announced
⏵ 2	2024-10-22 05:24:32	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Mycobacterium tuberculosis,H2S

Adrie J.C. Steyn
contact affiliation	1. Africa Health Research Institute, Durban, South Africa 2. 3Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA 3. Center for AIDS Research and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA
contact email	asteyn@uab.edu
lab head
Tafara Kunota
contact affiliation	Africa Health Research Institute
contact email	tafara.kunota@ahri.org
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/2021/08/PXD022969

PRIDE project URI

• PRIDE
  1. PXD022969
     1. Label: PRIDE project
     2. Name: Mycobacterium tuberculosis H2S functions as a sink to modulate central metabolism, bioenergetics, and drug susceptibility