Protein Homeostasis and Anti-Infectives

Pathogens rely on the host protein homeostasis machinery to support many of their protein folding and assembly reactions. In addition, pathogens often hijack host protein homeostasis machinery for alternative purposes. This reliance of pathogens on host protein homeostasis machinery presents novel opportunities for anti-infectives that function by modulating host chaperones and degradating enzymes in ways that are deleterious to the pathogen but tolerated by the host. A recent example is the testing of Hsp90 inhibitors being developed as anti-virals, specifically against Epstein-Barr Virus.

In addition to modulating of host protein homeostasis machinery as a new anti-infective strategy, another approach is to target essential components of pathogen protein homeostasis networks, taking advantage of differences from host machinery to achieve specificity.

Either of these approaches requires deep knowledge of the mechanisms of host and pathogen chaperones and degradation enzymes. The Protein Homeostasis group, in particular Vierling, Hebert, Gierasch and Chien, are exploring the potential of their research on chaperone mechanisms to develop novel anti-infectives, and are actively seeking partners in this effort.