LPS sugar chains vary widely in length and composition. They include an inner core (typically composed of Kdo and heptose sugars), a species-specific outer core, followed by a highly variable O-antigen. Hence, variability increases outward, with the inner components (e.g., the Lipid A disaccharide) more conserved and the outer O-antigen being the most variable region, even within the same species [266]. This diversity is relevant for the bacterial serotype determination and in particular for interactions with the immune system. The core sugars attached to LPS also act as a first barrier to the permeation of antibiotics . Lipid A, the bilayer-forming component of LPS, is relatively conserved but still modifiable through enzymatic modifications to alter immunogenicity and membrane properties. Figure illustrates how Lipid A can be altered through modifications at the level of the phosphate groups with either a small zwitterion or a sugar substituent, and variations in acyl chain numbers, impacting AMP resistance and the innate immune response. The considerable structural variability across all three LPS components, enabled by various enzymes, allows Gram-negative bacteria to adapt their outer membrane properties in response to environmental stresses, including antibiotic treatment .