Membrane vesicles (MVs) are naturally released by all bacteria as part of their normal growth and contain many of the components found in their parent bacterium, including DNA, RNA and proteins. Due to the immunogenic cargo associated with MVs, they contribute to mediating pathogenesis in their host. To date, we have limited knowledge regarding what regulates the cargo composition of bacterial MVs, in addition to whether MVs produced by Gram positive bacteria mediate pathogenesis.
We initially examined the role of bacterial growth stage on the proteome of Helicobacter pylori MVs and identified that bacterial growth stage affected the size, proteome, and immunogenicity of MVs. Moreover, we identified that the protein content of MVs is significantly different from that of their parent bacterium, suggesting that selection of protein cargo into MVs is regulated by bacterial growth. These findings identify a previously unknown role of bacterial growth stage on the proteome and the subsequent biological functions of MVs.
We next examined that ability of Gram positive MVs to mediate pathogenesis. To do this, we determined the ability of the Gram positive bacterium Staphylococcus aureus to produce MVs that contained immunogenic cargo. S. aureus MVs contained DNA, RNA and proteins and were capable of signalling via a range of innate immune receptors to mediate a host inflammatory response. Furthermore, upon entry of S. aureus MVs into epithelial cells, they activated the host intracellular degradation pathway of autophagy. This suggests that S. aureus MVs can mediate a pro-inflammatory response in the host via their immunogenic contents, and one intracellular, they are degraded by autophagy.
Collectively, these studies highlight the broad role of Gram positive and Gram negative MVs in mediating pathogenesis, and that the bacterial growth stage from which MVs are produced will impact their cargo composition and ultimately their biological functions.