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Modulation of host cell membrane nano-environment by mycobacterial glycolipids: Involvement of PI(4,5)P2 signaling lipid?

Abstract

Virulence-associated glycolipids from Mycobacterium tuberculosis (Mtb) act as effector molecules during infection—in addition to proteins. Upon insertion, they alter host cell membrane properties modifying host functions to impact Mtb survival and disease course. Here we combine tether force experiments and microscopy to reveal, previously unknown, insights on the potential involvement of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) lipid in Mtb lipid-host interaction landscape. Our data shows that Mtb lipids having different structural and chemical make-up distinctly alter host PI(4,5)P2 membrane abundance/organization and PI(4,5)P2-actin colocalization, thus impacting the plasma membrane-cytoskeletal adhesion forces. Combined with our previous findings that underscore the role of exogenous Mtb lipids in remodeling host plasma membrane organization and mechanics, this work builds upon a lipid-centric view of tubercular infections. Dynamically changing host plasma membrane lipid content–in response to virulent lipids–might represent a, so far unexplored, mechanism invoked by Mtb to modulate host cell adhesive properties to escape immune surveillance. These findings will deepen our collective understanding of the functional role of Mtb lipids in hijacking the host cell processes amenable to pharmacological inhibition.

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Supplementary files

Article information


Submitted
03 May 2020
Accepted
30 Jun 2020
First published
30 Jun 2020

Faraday Discuss., 2020, Accepted Manuscript
Article type
Paper

Modulation of host cell membrane nano-environment by mycobacterial glycolipids: Involvement of PI(4,5)P2 signaling lipid?

M. Mishra and S. Kapoor, Faraday Discuss., 2020, Accepted Manuscript , DOI: 10.1039/D0FD00051E

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