Exploiting and Subverting Tor Signaling in the Pathogenesis of Fungi, Parasites, and Viruses

In eukaryotes from yeast to humans, the Tor signaling cascade responds to nutrients and growth factors to orchestrate cell growth and proliferation. The central elements of this signaling cascade are the Tor protein kinases, which are the targets of the potent anti-proliferative and immunosuppressive natural product rapamycin [1]. Most organisms, including mammals, express a single Tor kinase; however, the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe contain two Tor homologs [2], and three and four (two classical Tor kinases and two Tor-like kinases) have been identified in the protozoans Leishmania major and Trypanosoma brucei, respectively [3,4]. The Tor kinases interact with other proteins to form two distinct and ubiquitously conserved complexes known as TORC1 and TORC2 (reviewed in [5]). Under optimal nutrient conditions, TORC2 drives actin polarization, whereas TORC1 promotes ribosome biogenesis and protein translation conducive to cell growth and proliferation while suppressing autophagy. In general, TORC1 is rapamycin sensitive in contrast to TORC2, which is resistant to rapamycin with the exception noted below for T. brucei [4,6]. This report discusses recent studies uncovering emerging roles for Tor signaling in promoting fungal and protozoan pathogen growth and proliferation tailored to invade and colonize the host. Moreover, protozoans and viruses have also developed strategies to subvert the host Tor signaling cascade and thereby commandeer the translational machinery to evade the immune system and promote viral protein synthesis, respectively.