Turning up Francisella pathogenesis: The LPS thermostat

摘要

The ability of microbes to adapt in response to an environmental change, such as the infection of a warm-blooded host is an important mechanism in pathogenesis. One major mechanism by which microbes respond to an environmental change is through the modification or remodeling of their membranes. Lipid A, or endotoxin, the bioactive component of lipopolysaccharide (LPS) is the major component of the outer leaflet of the outer membrane of Gram-negative bacteria. Lipid A, the membrane anchor of LPS is a (3-(1'-6)-linked glucosamine disaccharide backbone with amide linked fatty acids at the 2 and 2' positions, ester linked fatty acids at the 3 and 3' positions and terminal phosphate moieties at the 1 and 4' positions. Early steps in lipid A synthesis are conserved across Gram-negative species (Raetz pathway) though species-specific structural modifications are also observed. Modification of lipid A in response to environmental stressors such as pH, cation concentration, oxygen saturation and osmo-larity have been shown in a number of bacterial species to contribute to condition-specific membrane phenotypes. Temperature has also