What is it about?
Tuberculosis (TB) is a disease caused by the pathogen Mycobacterium tuberculosis (Mtb) and claims an estimated 1.6 million lives globally each year. This is despite the fact that both a vaccine and a treatment exist for this infection. So there is still a desperate need of improvement but research is very challenging in part due to how little we understand about the barriers (i.e. cell envelopes) preventing drugs entering the bacteria. Deciphering the molecular organization of cellular membranes remains a fundamental challenge. Molecular Dynamics simulations have brought a new level of understanding of these complex systems and how membrane components can interact together. Eukaryotic and bacterial membranes are now starting to reveal their molecular details but there is no accurate model of mycobacterial membranes. This relates to the complexity of lipids constituting these membranes. Especially, the role of the glycolipid phosphatidyl-myoinositol mannosides (PIMs) constituting more than 50% of the inner membrane of mycobacteria, remains elusive. Here, an international consortium composed by researchers from France, UK, US, and China, used multiscale molecular dynamics (MD) simulations to understand the structure-function relationship of the PIM lipid family and decipher how they self-organize to shape the inner membrane of mycobacteria. This model will help to better understand the biophysical properties of mycobacterial membranes and how this type of membrane may adapt to different bacterial growth conditions.
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Why is it important?
This model gives molecular insights on how mycobacterial membrane proteins can integrate into this very specific environment and how this membrane can modulate antibiotic diffusion.
Perspectives
This model will be especially useful in the context of drug discovery to develop new antibiotics to make sure they can pass through this barrier.
matthieu chavent
Our model of the mycobacterial cell membrane lets us understand how drugs may permeate through and kill pathogenic and drug-resistant mycobacterium tuberculosis.
Phill Stansfeld
University of Warwick
Read the Original
This page is a summary of: Supramolecular organization and dynamics of mannosylated phosphatidylinositol lipids in the mycobacterial plasma membrane, Proceedings of the National Academy of Sciences, January 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2212755120.
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