Journal article
Coxiella co-opts the Glutathione Peroxidase 4 to protect the host cell from oxidative stress–induced cell death
RK Loterio, DR Thomas, W Andrade, YW Lee, LL Santos, DPA Mascarenhas, TM Steiner, J Chiaratto, LF Fielden, L Lopes, LE Bird, GH Goldman, D Stojanovski, NE Scott, DS Zamboni, HJ Newton
Proceedings of the National Academy of Sciences of the United States of America | Published : 2023
Abstract
The causative agent of human Q fever, Coxiella burnetii, is highly adapted to infect alveolar macrophages by inhibiting a range of host responses to infection. Despite the clinical and biological importance of this pathogen, the challenges related to genetic manipulation of both C. burnetii and macrophages have limited our knowledge of the mechanisms by which C. burnetii subverts macrophages functions. Here, we used the related bacterium Legionella pneumophila to perform a comprehensive screen of C. burnetii effectors that interfere with innate immune responses and host death using the greater wax moth Galleria mellonella and mouse bone marrow–derived macrophages. We identified MceF (Mitocho..
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Grants
Awarded by National Institutes of Health
Funding Acknowledgements
We would like to kindly thank Prof. John Silke (Walter and Eliza Hall Institute of Medical Research, Australia) for providing lentiviral plasmids, and Prof. Robert Heinzen (Rocky Mountain Laboratories, NIH) for supplying C. burnetii genomic DNA and expression plasmids. We thank the team at the Biological Optical Microscopy Platform (University of Melbourne) and the Melbourne Cytometry Platform (Doherty Institute node, University of Melbourne) who provided invaluable technical expertise and maintenance for the confocal microscope and cytometry used in this study. The Australian Genome Research Facility provided sequencing services in Melbourne. We thank Prof Mike Ryan for gifting to the Stojanovski Lab the Mfn2 and NDUFAF2 antibodies. We thank the Laboratory Managers Maira Nakamura and Livia Marangoni Alfaya for technical support. R.K.L. was a graduate student at the Basic and Applied Immunology Program from the Medical School of Ribeirao Preto, University of Sao Paulo, Brazil, and recipient of the fellowships (2016/24275-7 and 2018/236898) from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP). This work was supported by grants from the Center for Research on Inflammatory Diseases (CRID/FAPESP, grant 2013/08216-2), FAPESP (grants 2014/04684-4, 2019/11342-6, and 2016/07870-9) and NHMRC Ideas Grant 2010841. G.H.G. and D.S.Z. are 1A and 1B Research Fellows from CNPq, respectively.