Pathways Used By Bacteria in Outer Membrane Vesicle Toxicity: A Target for Disease Treatment

摘要

In recent years bacterial resistance to antibiotics has increased; leading to a higher demand for antibiotic alternatives. Our lab is exploring alternative treatment methods which target the bacterial virulence mechanism. One mechanism of toxin delivery to host cells is outer membrane vesicles (OMVs). They are created by gram-negative bacteria as a stress response by blebbing off their outer membrane to form vesicles with a diameter of 10-300nm. OMVs are used by bacteria in delivery and communication. We have investigated the mechanism of delivery for OMVs to their host cells. Aggregatibacter actinomycetemcomitans (A.a.), a gram-negative bacteria which causes periodontitis and endocarditis in humans, produces outer membrane vesicles. LtxA is a toxin know to be released by A.a. both by secretion and by association with OMVs. Since it is known that free LtxA relies on the LFA-1 receptor and cholesterol for host toxicity we investigated the importance of these factors in OMV associated LtxA.