PXD027875

PXD027875 is an original dataset announced via ProteomeXchange.

Title	Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic effects of lysolipids
Description	Mycobacterium tuberculosis (M.tb) resides in human macrophages where it exploits host lipids for survival. Little is known about the interaction between M.tb and macrophage plasmalogens, the subclass of glycerophospholipids having a vinyl-ether bond at sn-1. Lysoplasmalogens, produced from plasmalogens by hydrolysis at sn-2 by PLA2, are potentially toxic, but can be broken down by host lysoplasmalogenase, an integral membrane protein of the YhhN family that hydrolyzes the vinyl ether bond at sn-1 to release a fatty aldehyde and glycerophospho-ethanolamine or –choline. Curiously, M.tb encodes its own YhhN protein (MtbYhhN) despite having no endogenous plasmalogens. Here, the gene for MtbYhhN (Rv1401) was cloned and expressed in Mycobacterium smegmatis (M.smeg), and the partially purified protein exhibited abundant lysoplasmalogenase activity that was specific for lysoplasmenylethanolamine (pLPE) or lysoplasmenylcholine (pLPC) (Vmax~15.5 mol/min/mg; Km~83 M). Based on monitoring cell density by OD600, pLPE, pLPC, lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) were not toxic to intact M.smeg cells, but pLPC and LPC were highly toxic to M.smeg spheroplasts, which are cell wall deficient (CWD) forms that lack the bacterial wall. Importantly, spheroplasts prepared from M.smeg cells overexpressing MtbYhhN were protected from membrane disruption/lysis by pLPC (but not by LPC), which was rapidly depleted from the media. Finally, overexpression of full-length MtbYhhN in M.smeg increased its survival within human macrophages by 2.6-fold compared to vector control at 24 h. These data provide support for the hypothesis that MtbYhhN protein confers a mycobacterial growth advantage in macrophages by cleaving toxic pLPC from the host cells into potentially energy-producing products.
HostingRepository	PRIDE
AnnounceDate	2022-05-20
AnnouncementXML	Submission_2022-05-20_03:39:25.978.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Mycobacterium tuberculosis; NCBI TaxID: 1773;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-11 22:14:43	ID requested
⏵ 1	2022-05-20 03:39:26	announced

Jurkowitz MS, Azad AK, Monsma PC, Keiser TL, Kanyo J, Lam TT, Bell CE, Schlesinger LS, Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic host lysolipids. J Biol Chem, 298(5):101849(2022) [pubmed]

submitter keyword: Mycobacterium tuberculosis Rv1401 gene, Mycobacterium smegmatis, lysoplasmalogenase, YhhN protein, macrophage, Phospholipase A, lysoplasmalogen, cell injury and protection, spheroplasts, cell-wall-deficient (CWD), lysophospholipids

TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027875
     1. Label: PRIDE project
     2. Name: Mycobacterium tuberculosis encodes a YhhN family membrane protein with lysoplasmalogenase activity that protects against toxic effects of lysolipids