Adapting Architecture: Lipid Membrane Remodeling in Mycobacteria

The mycobacterial cell envelope is a formidable barrier, regarded as one of the most chemically and structurally elaborate architectures in the Bacteria kingdom. Membrane remodeling, defined as changes in membrane lipid composition in response to stressors, has been a subject of broad investigation because of its implications for permeability, antibiotic susceptibility, immunogenicity, and virulence. However, because remodeling is a highly dynamic process governed by multiple, deeply interconnected cellular response pathways, its underlying mechanisms and biophysical consequences remain incompletely understood. In this review, we synthesize the current knowledge of how the composition and organization of membrane lipids shift under physiologically relevant conditions, and we examine how these changes intersect with key stress response pathways. As a unifying thread connecting lipid composition, envelope architecture, and cellular function, we summarize our understanding of mycobacterial membrane biophysical properties, highlighting recent advances as well as conceptual and methodological gaps that remain in the field.