bioRxiv Science⌕ Search

Biology subjects

Maalej, M.

Publications and source records attributed to Maalej, M..

2 recordsLinked to original sources

Lipopolysaccharides nanodiscs, a biomimetic platform to study bacterial surface.

Lipopolysaccharides (LPS) are essential components of the outer membranes of Gram-negative bacteria, playing a crucial role in antimicrobial resistance, virulence, and the hosts immune response. Self-assembled particles displaying LPS are essential for biophysical studies addressing the behavior of bacterial surfaces under specific biomimetic conditions. Styrene-maleic acid (SMA) copolymers were employed to form LPS nanodiscs, either from extracted LPS or directly from purified outer membranes. These nanodiscs, derived from pathogenic O157:H7 or laboratory E. coli strains, are well-defined in size and yield high-resolution nuclear magnetic resonance (NMR) spectra. They have been successfully used to investigate molecular recognition by a human C-type Lectin Receptor (CLR) of the immune system and interaction with polymyxin antibiotics using various biophysical methods. This study high-lights the significance of LPS nanodiscs as bacterial surface mimetics and opens promising avenues for further research into LPS structure and interactions. The ability to generate well-defined LPS nanodiscs offers a powerful tool for studying the molecular mechanisms underlying bacterial pathogenesis and immune response.

biophysics↗

The unique three-dimensional arrangement of Macrophage Galactose Lectin enables E. coli LipoPolySaccharides recognition through two distinct interfaces

LipoPolySaccharides are a hallmark of Gram-negative bacteria and their presence at the cell surface is key for bacterial integrity. As surface exposed components, they are recognized by immunity C-type lectin receptors present on Antigen Presenting Cells. Human Macrophage Galactose Lectin binds E. coli surface that presents a specific glycan motif. Nevertheless, this high affinity interaction occurs regardless of the integrity of its canonical calcium-dependent glycan binding site. Nuclear Magnetic Resonance of MGL carbohydrate recognition domain and complete extracellular domain revealed a new glycan binding site opposite to the canonical site. A model of trimeric Macrophage Galactose Lectin was determined based on a combination of Small Angle X-ray scattering and Alphafold. A disulphide bond positions the Carbohydrate Recognition Domain perpendicular to the coiled-coil domain. This unique configuration for a C-type lectin orients the six glycan sites of MGL in an ideal position to bind LipoPolySaccharides at the bacterial surface with high avidity.

biophysics↗