Lipopolysaccharide
(LPS) is a crucial constituent of the outer
membrane of most Gram-negative bacteria, playing a fundamental role
in the protection of bacteria from environmental stress factors, in
drug resistance, in pathogenesis, and in symbiosis. During the last
decades, LPS has been thoroughly dissected, and massive information
on this fascinating biomolecule is now available. In this Review,
we will give the reader a third millennium update of the current knowledge
of LPS with key information on the inherent peculiar carbohydrate
chemistry due to often puzzling sugar residues that are uniquely found
on it. Then, we will drive the reader through the complex and multifarious
immunological outcomes that any given LPS can raise, which is strictly
dependent on its chemical structure. Further, we will argue about
issues that still remain unresolved and that would represent the immediate
future of LPS research. It is critical to address these points to
complete our notions on LPS chemistry, functions, and roles, in turn
leading to innovative ways to manipulate the processes involving such
a still controversial and intriguing biomolecule.