Gram-Negative Extremophile Lipopolysaccharides: Promising Source of Inspiration for a New Generation of Endotoxin Antagonists

Extremophiles are microorganisms exhibiting the fascinating capability to thrive in habitats that are considered clearly inhospitable. Extreme-loving microorganisms have acquired ever-increasing importance in the biomedical and pharmaceutical fields, with many of their bioactive products having long been used as life-saving drugs. In this context, extremophile Gram-negative bacterial lipopolysaccharides (LPSs) and their analogues offer many promising opportunities for a variety of biomedical and therapeutic applications. The structure-dependent capability to elicit and to modulate host immune responses is surely the most intriguing feature of LPSs in the context of new drug discovery and design. This review offers an overview of the chemical peculiarities of LPSs isolated from extremophile bacteria, providing the most promising results relating to their biological activity. We discuss the pharmacologically important potential of extremophile LPSs as fundamental immunomodulatory compounds from the perspective of drug synthesis and development.