Lipopolysaccharide composition determines the entry kinetics of bacterial outer membrane vesicles into host cells

O'Donoghue, Eloise Jasmin (2018). Lipopolysaccharide composition determines the entry kinetics of bacterial outer membrane vesicles into host cells. University of Birmingham. Ph.D.

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Abstract

Outer membrane vesicles (OMVs) are nanosized proteoliposomes ubiquitously released from the outer membrane of Gram negative bacteria, and are known to contribute to immune priming and disease pathogenesis. However, the current understanding of their interactions with host cells is limited by a lack of methods to study the rapid kinetics of vesicle entry and cargo delivery. This work has developed a highly sensitive method to study vesicle entry into host cells in real-time using a genetically encoded, vesicle targeted probe. Using this approach, it was found that the route of vesicular uptake, and thus entry kinetics and efficiency, are shaped by bacterial cell wall composition. The presence of O polysaccharide in lipopolysaccharide creates a bias towards non-receptor mediated endocytosis, which enhances both the rate and efficiency of entry into host cells. This work indicates that the composition of the bacterial cell wall influences the behaviour of OMVs, and is therefore implicated in secretion-system independent delivery of bacterial virulence factors during Gram negative infection.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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