Interplay between Outer Membrane Vesicles and Host Defense Peptides

Summary

The scope of this thesis is the interplay between Host Defense Peptides (HDPs) and Outer Membrane Vesicles (OMVs). HDPs have both antimicrobial and immunomodulatory properties. OMVs contain multiple antigens in their native environment and are therefore promising for vaccine development. It was also thought that OMVs could protect bacteria against killing by HDPs, which was described before, but additionally it was investigated whether OMV release could be a response of bacteria upon HDPs in the environment. This increase in OMV yield could also be used for vaccine production, if OMV properties are not significantly altered. HDPs are known to have membrane-active properties, but the role of LPS-binding in killing of Gram-negative bacteria is not yet evident. Therefore, LPS-binding was correlated with HDP antibacterial effectivity, to distinguish between LPS acting as anchor and facilitating HDP functions or LPS acting as a sink and inhibiting HDP functions. Furthermore, immunomodulatory capabilities of HDPs were investigated, since HDPs are known to neutralize LPS-induced toll-like receptor (TLR) 4 activation but this neutralization has not yet been described for OMV-induced activation. If HDPs could balance OMV-induced immune responses, the combination could be promising for vaccine development.

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