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.

Mycobacterial lipid-derived immunomodulatory drug- liposome conjugate eradicates endosome-localized mycobacteria.

Tuberculosis is a challenging disease due to the intracellular residence of its pathogen, Mycobacterium tuberculosis, and modulation of the host bactericidal responses. Lipids from Mycobacterium tuberculosis regulate macrophage immune responses dependent on the infection stage and intracellular location. We show that liposomes constituted with immunostimulatory lipids from mycobacteria modulate the cellular immune response and synergize with sustained drug delivery for effective pathogen eradication.

Lipidomic and Membrane Mechanical Signatures in Triple-Negative Breast Cancer: Scope for Membrane-Based Theranostics.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer associated with poor prognosis, higher grade, and a high rate of metastatic occurrence. Limited therapeutic interventions and the compounding issue of drug resistance in triple-negative breast cancer warrants the discovery of novel therapeutic targets and diagnostic modules. To this view, in addition to proteins, lipids also regulate cellular functions via the formation of membranes that modulate membrane protein function, diffusion, and their localization; thus, orchestrating signaling hot spots enriched in specific lipids/proteins on cell membranes.

Ligand Induced Cu Transport Restricts Cancer and Mycobacterial Growth: Towards a Plug-and-Select Ion Channel Scaffold.

Synthetic channels with high ion selectivity are attractive drug targets for diseases involving ion dysregulation. Achieving selective transport of divalent ions is highly challenging due their high hydration energies. A small tripeptide amphiphilic scaffold installed with a pybox ligand selectively transports Cu ions across membranes.

Various Facets of Pathogenic Lipids in Infectious Diseases: Exploring Virulent Lipid-Host Interactome and Their Druggability.

Lipids form an integral, structural, and functional part of all life forms. They play a significant role in various cellular processes such as membrane fusion, fission, endocytosis, protein trafficking, and protein functions. Interestingly, recent studies have revealed their more impactful and critical involvement in infectious diseases, starting with the manipulation of the host membrane to facilitate pathogenic entry.

Mycobacterium Lipids Modulate Host Cell Membrane Mechanics, Lipid Diffusivity, and Cytoskeleton in a Virulence-Selective Manner.

Microbial lipids play a critical role in the pathogenesis of infectious diseases by modulating the host cell membrane properties, including lipid/protein diffusion and membrane organization. () synthesizes various chemically distinct lipids that are exposed on its outer membrane and interact with host cell membranes. However, the effects of the structurally diverse lipids on the host cell membrane properties to fine-tune the host cellular response remain unknown.

A Virulence-Associated Glycolipid with Distinct Conformational Attributes: Impact on Lateral Organization of Host Plasma Membrane, Autophagy, and Signaling.

() serves as the epitome of how lipids-next to proteins-are utilized as central effectors in pathogenesis. It synthesizes an arsenal of structurally atypical lipids (C60-C90) to impact various membrane-dependent steps involved in host interactions. There is a growing precedent to support insertion of these exposed lipids into the host membrane as part of their mode of action.

Dynamic Remodeling of the Host Cell Membrane by Virulent Mycobacterial Sulfoglycolipid-1.

Lipids dictate membrane properties to modulate lateral membrane organization, lipid/protein diffusion and lipid-protein interactions, thereby underpinning proper functioning of cells. Mycobacterium tuberculosis harnesses the power of its atypical cell wall lipids to impact immune surveillance machinery centered at the host cell membrane. However, the role of specific virulent lipids in altering host cellular functions by modulating membrane organization and the associated signaling response are still pertinent unresolved questions.

Biophysical characterization of mycobacterial model membranes and their interaction with rifabutin: Towards lipid-guided drug screening in tuberculosis.

Lipid structure critically dictates the molecular interactions of drugs with membranes influencing passive diffusion, drug partitioning and accumulation, thereby underpinning a lipid-composition specific interplay. Spurring selective passive drug diffusion and uptake through membranes is an obvious solution to combat growing antibiotic resistance with minimized toxicities. However, the spectrum of complex mycobacterial lipids and lack thereof of suitable membrane platforms limits the understanding of mechanisms underlying drug-membrane interactions in tuberculosis.