Fusion Landscape of Mycobacterial Envelope-Derived Lipid Vesicles with Intact Bacteria Dictates High Intracellular Drug Retention

Membrane vesicles are critical regulators of pathogenic diseases. In tubercular infections, the use of mycobacteria derived vesicles as delivery vehicles to overcome drug resistance and complex treatment regimens has never been attempted. Here, we first address how these vesicles interact with their target cells, especially via membrane fusion. Membrane fusion between alike mycobacterial outer and inner membrane layer-derived lipid vesicles is shown to be driven by the structural, geometrical, and biophysical attributes of constituent lipids. The increased fusion of outer-membrane-derived vesicles with intact bacteria ensures enhanced intracellular drug levels and is presented as a “natural” antitubercular drug delivery vehicle.