Summary: H O S T - P A T H O G E N I N T E R A C T I O N S
Trypanosoma cruzi Targets Akt in Host Cells as an
Intracellular Antiapoptotic Strategy
Marina V. Chuenkova and Mercio PereiraPerrin*
(Published 17 November 2009; Volume 2 Issue 97 ra74)
The parasite Trypanosoma cruzi, which causes Chagas' disease, differentiates in the cytosol of its
host cell and then replicates and spreads infection, processes that require the long-term survival of
the infected cells. Here, we show that in the cytosol, parasite-derived neurotrophic factor (PDNF), a
trans-sialidase that is located on the surface of T. cruzi, is both a substrate and an activator of the
serine-threonine kinase Akt, an antiapoptotic molecule. PDNF increases the expression of the gene
that encodes Akt while suppressing the transcription of genes that encode proapoptotic factors. Con-
sequently, PDNF elicits a sustained functional response that protects host cells from apoptosis induced by
oxidative stress and the proinflammatory cytokines tumor necrosis factor­a and transforming growth
factor­b. Given that PDNF also activates Akt by binding to the neurotrophic surface receptor TrkA, we pro-
pose that this protein activates survival signaling both at the cell surface, by acting as a receptor-binding
ligand, and inside cells, by acting as a scaffolding adaptor protein downstream of the receptor.
INTRODUCTION
Chagas'disease can afflict patients for many years or even decades and com-
monly starts when the obligate intracellular parasite Trypanosoma cruzi
gains access to cells in the skin or in the mucosa after release from reduviid

Source: Arnold, Jonathan - Nanoscale Science and Engineering Center & Department of Genetics, University of Georgia

Collections: Biotechnology