PITHER, MOLLY DOROTHY (2022) The elucidation of the chemical structure of Lipopolysaccharides and other glycoconjugates isolated from bacteria of the Human Microbiota. [Tesi di dottorato]

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The human intestinal tract is home to an extensive community of bacteria that have coevolved to thrive within such a complex and highly competitive niche. This massive consortium of bacteria, known as the gut microbiota (GM), is essential to the health and well-being of the host. Many of the species of the GM are Gram-negative which characteristically have a particular outer membrane covered by a layer of glycoconjugates known as the lipopolysaccharide (LPS). LPS are widely known for their structure-dependent immunostimulatory properties, that are related to the ability to activate a pro-inflammatory response in humans once recognized by the innate immune receptor complex Toll-Like receptor 4 (TLR4)/Myeloid Differentiation factor-2 (MD-2). 1 On the other hand, some other LPS structures act as inhibitory agents by preventing the binding of pro-inflammatory LPS to MD-2/TLR4, and therefore inhibiting or dampening the dangerous effects on infected cells. This PhD project aims to characterise multiple LPS from different bacterial species known to colonise the human gut and uncover the chemistry of the LPS from these symbiotic microbes. This work will then lead to investigations into how the LPS structures from beneficial species are recognised by the host immune system in a different manner than pathogenic LPS.

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