The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
Alessandro D Uboldi
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
Alexandra Garnham
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
Magdalena Franco
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
Nicole D Marino
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
Michael W Panas
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
Nuffield Department of Clinical Laboratory Science, Oxford University, John Radcliffe Hospital, Oxford, United Kingdom
Marta Enciso
La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
Matthew T O'Neill
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Sash Lopaticki
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Rebecca J Stewart
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
Grant Dewson
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Mathematics and Statistics, The University of Melbourne, Melbourne, Australia
Brian J Smith
La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia
Seth L Masters
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
John C Boothroyd
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, The University of Melbourne, Melbourne, Australia
Infection by Toxoplasma gondii leads to massive changes to the host cell. Here, we identify a novel host cell effector export pathway that requires the Golgi-resident aspartyl protease 5 (ASP5). We demonstrate that ASP5 cleaves a highly constrained amino acid motif that has similarity to the PEXEL-motif of Plasmodium parasites. We show that ASP5 matures substrates at both the N- and C-terminal ends of proteins and also controls trafficking of effectors without this motif. Furthermore, ASP5 controls establishment of the nanotubular network and is required for the efficient recruitment of host mitochondria to the vacuole. Assessment of host gene expression reveals that the ASP5-dependent pathway influences thousands of the transcriptional changes that Toxoplasma imparts on its host cell. All these changes result in attenuation of virulence of Δasp5 tachyzoites in vivo. This work characterizes the first identified machinery required for export of Toxoplasma effectors into the infected host cell.
