Journal article
Lysosomal degradation products induce Coxiella burnetii virulence
P Newton, DR Thomas, SCO Reed, N Lau, B Xu, SY Ong, S Pasricha, PB Madhamshettiwar, LE Edgington-Mitchell, KJ Simpson, CR Roy, HJ Newton
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2020
Abstract
Coxiella burnetii is an intracellular pathogen that replicates in a lysosome-like vacuole through activation of a Dot/Icm-type IVB secretion system and subsequent translocation of effectors that remodel the host cell. Here a genome-wide small interfering RNA screen and reporter assay were used to identify host proteins required for Dot/Icm effector translocation. Significant, and independently validated, hits demonstrated the importance of multiple protein families required for endocytic trafficking of the C. burnetii-containing vacuole to the lysosome. Further analysis demonstrated that the degradative activity of the lysosome created by proteases, such as TPP1, which are transported to the..
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Awarded by University of Melbourne
Funding Acknowledgements
Confocal microscopy was performed at the Biological Optical Microscopy Platform, The University of Melbourne (https://microscopy.unimelb.edu.au/). We thank Dan Thomas and Jennii Luu from the Victorian Centre for Functional Genomics for expert technical help during the screen. We acknowledge use of the services and facilities of the Australian Genome Research Facility. Single-copy integration plasmids were a gift from P. A. Beare and R. A. Heinzen, Rocky Mountain Laboratories, NIH. This research was supported by Australian National Health andMedical Research Council APP1063646 and APP1120344. The Victorian Centre for Functional Genomics (K.J.S.) is funded by the Australian Cancer Research Foundation, the Australian Phenomics Network through funding from the Australian Government's National Collaborative Research Infrastructure Strategy Program, and the Peter MacCallum Cancer Centre Foundation. L.E.E.-M. is funded by the Grimwade Fellowship from the Russell and Mab Grimwade Miegunyah Fund at The University of Melbourne and a Discovery Early Career Researcher Award Fellowship from the Australian Research Council (DE180100418).