Hsp90 Plays a Role in Host-Bacterial Interactions: Insight Gained from Acanthamoeba castellanii

The selective pressures they are faced with, both inside and outside their hosts, shape pathogens. Facultative intracellular organisms, including Legionella, Mycobacterium and many other pathogens, encounter amoebal predators in nature and this interaction leads to acquisition of novel genetic material that facilitates their ability to infect both amoebae and higher order species. Understanding these interactions that are continuously occurring in the environment provides an opportunity to obtain greater insight into the mechanisms of pathogenesis, particularly because these relationships are most often between single-celled organisms, making them more amenable to genetic analyses as compared to more complex multi-cellular creatures. We utilized the single celled virulence model for Legionella and Mycobacterium, the environmental amoeba Acanthamoeba castellanii, to identify bacterial and host genes required for pathogenesis and susceptibility/resistance to infection, respectively. In this chapter, we will focus on our intriguing observation that decreased expression of Hsp90, a molecular chaperone involved in host cell signaling and protein targeting, increases resistance to host cell infection by pathogenic bacteria.