Chemical remodeling of the mycomembrane with chain-truncated lipids sensitizes mycobacteria to rifampicin

The outer mycomembrane of Mycobacterium tuberculosis and related pathogens is a robust permeability barrier that protects against antibiotic treatment. Here, we demonstrate that synthetic analogues of the mycomembrane biosynthetic precursor trehalose monomycolate bearing truncated lipid chains incre...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2023-11, Vol.59 (93), p.13859-13862
Main Authors: Gaidhane, Ishani V, Biegas, Kyle J, Erickson, Helen E, Agarwal, Prachi, Chhonker, Yashpal S, Ronning, Donald R, Swarts, Benjamin M
Format: Article
Language:English
Subjects:
Cell Membrane - chemistry
Cell Wall
Lipids
Lipids - analysis
Mycobacterium tuberculosis - chemistry
Permeability
Rifampin - pharmacology
Trehalose
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Summary:The outer mycomembrane of Mycobacterium tuberculosis and related pathogens is a robust permeability barrier that protects against antibiotic treatment. Here, we demonstrate that synthetic analogues of the mycomembrane biosynthetic precursor trehalose monomycolate bearing truncated lipid chains increase permeability of Mycobacterium smegmatis cells and sensitize them to treatment with the first-line anti-tubercular drug rifampicin. The reported strategy may be useful for enhancing entry of drugs and other molecules to mycobacterial cells, and represents a new way to study mycomembrane structure and function. Remodeling the notoriously impenetrable mycobacterial outer membrane with synthetic lipids enhances cellular permeability, sensitizing bacteria to the clinically used antibiotic rifampicin.
ISSN:1359-7345
1364-548X
1364-548X
DOI:10.1039/d3cc02364h