Di Lorenzo, Flaviana (2014) Chemical Structure of cell-wall components isolated from pathogen bacteria. [Tesi di dottorato]

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Abstract

The aim of the present PhD thesis is the extraction, purification and structural elucidation of lipopolysaccharides (LPS) isolated from human pathogen bacteria. LPSs are amphiphilic macromolecules that compose about 75% of the outer membrane of Gram-negative bacteria that are indispensable for the growth and the survival of bacteria. LPS elicits a potent host innate immune response through the TLR4 and MD-2 receptorial complex expressed on diverse phagocytic cells. This recognition is crucial since excessive exposure (or excessive responses) to LPS can lead to an uncontrolled inflammation process, as in case of individuals affected by Cystic Fibrosis (CF) in which premature death occurs after a chronic inflammation state. The basic genetic defect predisposes CF patients to recurrent pulmonary infections that are the major cause of morbidity and mortality in CF. Characteristic CF pathogens include Pseudomonas aeruginosa, bacteria belonging to the Burkholderia cepacia complex (BCC) and the newly identified genus Pandoraea. Since LPS is involved in elicitation of host innate immune response in a structure-dependent mode, the investigation of the LPS structure is mandatory to understand the virulence of the abovementioned microorganisms. A little section of the present PhD work has been also dedicated to the structural elucidation of LPS isolated from extremophilic bacteria since it was previously demonstrated that LPSs from non-pathogenic bacteria exert antagonist or partial antagonist activity towards toxic LPSs. Thus, the structural characterisation of extremophiles LPS represents a new perspective for treatment of pathologies caused or exacerbated by bacterial LPS, such as in case of cystic fibrosis disease.

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