Effects of Membrane Lipid Composition on Mycobacterium Tuberculosis EsxA Membrane Insertion: A Dual Play of Fluidity and Charge

Overview

Journal Tuberculosis (Edinb)

Specialties Infectious Diseases
Pulmonary Medicine

Date 2019 Aug 21

PMID 31430698

Citations 10

Authors

Supriyo Ray

Salvador Vazquez Reyes

Chuan Xiao

Jianjun Sun

Affiliations

Soon will be listed here.

Abstract

As a key virulence factor of Mycobacterium tuberculosis, EsxA or 6-kDa early secreted antigenic target (ESAT-6) has been implicated in phagosome rupture and mycobacterial translocation from the phagosome to the cytosol within macrophages. Our previous studies have shown that EsxA permeabilizes liposomal membrane at acidic pH and a membrane-permeabilization defective mutant Q5K attenuates mycobacterial cytosolic translocation and virulence in macrophages. To further probe the mechanism of EsxA membrane permeabilization, here we characterized the effects of various lipid compositions, including biologically relevant phagosome-mimicking lipids and lipid rafts, on the structural stability and membrane insertion of EsxA WT and Q5K. We have found a complex dual play of membrane fluidity and charge in regulating EsxA membrane insertion. Moreover, Q5K affects the membrane insertion through a structure- and lipid composition-independent mechanism. The results of this study provide a novel insights into the mechanism of EsxA membrane interaction.

Citing Articles

A Small Protein but with Diverse Roles: A Review of EsxA in Mycobacterium-Host Interaction.

Bao Y, Wang L, Sun J Cells. 2021; 10(7).

PMID: 34209120 PMC: 8305481. DOI: 10.3390/cells10071645.

A Fluorescence Dequenching-based Liposome Leakage Assay to Measure Membrane Permeabilization by Pore-forming Proteins.

Aguilera J, Vazquez-Reyes S, Sun J Bio Protoc. 2021; 11(10):e4025.

PMID: 34150932 PMC: 8187125. DOI: 10.21769/BioProtoc.4025.

Mitochondria: Powering the Innate Immune Response to Mycobacterium tuberculosis Infection.

Patrick K, Watson R Infect Immun. 2021; 89(4).

PMID: 33558322 PMC: 8090963. DOI: 10.1128/IAI.00687-20.

Development of an In Vitro Membrane Model to Study the Function of EsxAB Heterodimer and Establish the Role of EsxB in Membrane Permeabilizing Activity of .

Vazquez Reyes S, Ray S, Aguilera J, Sun J Pathogens. 2020; 9(12).

PMID: 33276541 PMC: 7761419. DOI: 10.3390/pathogens9121015.

Host Cell Targets of Released Lipid and Secreted Protein Effectors of .

Augenstreich J, Briken V Front Cell Infect Microbiol. 2020; 10:595029.

PMID: 33194845 PMC: 7644814. DOI: 10.3389/fcimb.2020.595029.

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