PXD010726

PXD010726 is an original dataset announced via ProteomeXchange.

Title	Metabolism of host-derived glycolytic products by Mycobacterium tuberculosis requires five metabolic pathways
Description	Bacterial nutrition is a key aspect of host-pathogen interaction and bacteria must adapt to use nutrients available in the host. Lipid droplets-derived fatty acids are considered the major intracellular carbon source for Mycobacterium tuberculosis (Mtb), an intracellular pathogen causing Tuberculosis disease. However, many other (and more soluble) substrates are available in vivo and may represent alternative carbon sources. Lactate and pyruvate are rather abundant in human cells and fluids and represent two possible candidates. In this work, we employed a “multi-omics” approach (Transposon Directed Insertion Site Sequencing (TraDIS), RNA-seq transcriptomics, proteomics and stable isotopic labelling coupled with mass spectrometry-based metabolomics) and classic microbial physiology to study Mtb metabolism of lactate and pyruvate. We discovered that Mtb is well adapted to use lactate and pyruvate as sole carbon sources and that it requires gluconeogenesis, Krebs cycle, GABA shunt, glyoxylate shunt and methylcitrate cycle for their metabolism. These latter are traditionally associated with fatty acid metabolism and unexpectedly, we found that methylcitrate cycle operates in reverse. This latter discovery changes the role of this pathway making it a direct route for the biosynthesis of propionyl-CoA, the essential precursor for the biosynthesis of odd-chain fatty acids, abundantly present in Mtb cell envelope.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_12:19:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Steven Howell
SpeciesList	scientific name: Mycobacterium tuberculosis H37Rv; NCBI TaxID: 83332;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-08 08:43:57	ID requested
⏵ 1	2020-05-26 12:19:42	announced

Serafini A, Tan L, Horswell S, Howell S, Greenwood DJ, Hunt DM, Phan MD, Schembri M, Monteleone M, Montague CR, Britton W, Garza-Garcia A, Snijders AP, VanderVen B, Gutierrez MG, West NP, de Carvalho LPS, Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism. Mol Microbiol, 112(4):1284-1307(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Mycobacterium tuberculosis, bacterial nutrition, glucose metabolism, LC-MSMS, TMT, Orbitrap

Bram Snijders
contact affiliation	Mass Spectrometry and Proteomics Science Technology Platform, Francis Crick Institute, LONDON NW1 1AT, UK
contact email	bram.snijders@crick.ac.uk
lab head
Steven Howell
contact affiliation	Francis Crick Institute
contact email	steven.howell@crick.ac.uk
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/2020/05/PXD010726

PRIDE project URI

• PRIDE
  1. PXD010726
     1. Label: PRIDE project
     2. Name: Metabolism of host-derived glycolytic products by Mycobacterium tuberculosis requires five metabolic pathways