Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells.

Outer membrane vesicles are nano-sized microvesicles shed from the outer membrane of Gram-negative bacteria and play important roles in immune priming and disease pathogenesis. However, our current mechanistic understanding of vesicle-host cell interactions is limited by a lack of methods to study the rapid kinetics of vesicle entry and cargo delivery to host cells. Here, we describe a highly sensitive method to study the kinetics of vesicle entry into host cells in real-time using a genetically encoded, vesicle-targeted probe. We found that the route of vesicular uptake, and thus entry kinetics and efficiency, are shaped by bacterial cell wall composition. The presence of lipopolysaccharide O antigen enables vesicles to bypass clathrin-mediated endocytosis, which enhances both their entry rate and efficiency into host cells. Collectively, our findings highlight the composition of the bacterial cell wall as a major determinant of secretion-independent delivery of virulence factors during Gram-negative infections.

Citation

Eloise J O'Donoghue, Natalie Sirisaengtaksin, Douglas F Browning, Ewa Bielska, Mohammed Hadis, Francisco Fernandez-Trillo, Luke Alderwick, Sara Jabbari, Anne Marie Krachler. Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells. PLoS pathogens. 2017 Nov 29;13(11):e1006760

PMID: 29186191

search → result