From Molecular Dynamics to Supramolecular Organization: The Role of PIM Lipids in the Originality of the Mycobacterial Plasma Membrane - Laboratoire de Physique Théorique - LPT Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2022

From Molecular Dynamics to Supramolecular Organization: The Role of PIM Lipids in the Originality of the Mycobacterial Plasma Membrane

Chelsea Brown
  • Fonction : Auteur
Robin Corey
Ya Gao
  • Fonction : Auteur
Yeol Kyo Choi
  • Fonction : Auteur
Elizabeth Fullam
  • Fonction : Auteur
Wonpil Im
Phillip Stansfeld

Résumé

Abstract Mycobacterium tuberculosis ( Mtb ) is the causative agent of tuberculosis, a disease that claims ~1.5 million lives annually. The current treatment regime is long and expensive, and missed doses contribute to drug resistance. There is much to be understood about the Mtb cell envelope, a complicated barrier that antibiotics need to negotiate to enter the cell. Within this envelope, the plasma membrane is the ultimate obstacle and is proposed to be comprised of over 50% mannosylated phosphatidylinositol lipids (phosphatidyl- myo inositol mannosides, PIMs), whose role in the membrane structure remains elusive. Here we used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to drive biophysical properties of the Mycobacterial plasma membrane. To validate the model, we tested known anti-tubercular drugs and replicated previous experimental results. Our results shed new light into the organization of the Mycobacterial plasma membrane and provides a working model of this complex membrane to use for in silico studies. This opens the door for new methods to probe potential antibiotic targets and further understand membrane protein function. Abstract Figure

Dates et versions

hal-03818971 , version 1 (18-10-2022)

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Chelsea Brown, Robin Corey, Ya Gao, Yeol Kyo Choi, Martine Gilleron, et al.. From Molecular Dynamics to Supramolecular Organization: The Role of PIM Lipids in the Originality of the Mycobacterial Plasma Membrane. 2022. ⟨hal-03818971⟩
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