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Neutrophils use selective autophagy receptor p62 to target Staphylococcus aureus for degradation in the zebrafish model

View ORCID ProfileJosie F Gibson, View ORCID ProfileTomasz K Prajsnar, Justyna J Serba, Rebecca D Tonge, View ORCID ProfileAndrew J Grierson, View ORCID ProfilePhilip W Ingham, View ORCID ProfileStephen A Renshaw, View ORCID ProfileSimon A Johnston
doi: https://doi.org/10.1101/604884
Josie F Gibson
1Department of Infection, Immunity and Cardiovascular disease, Medical School, University of Sheffield, S10 2TN, UK
2The Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK
3Institute of Molecular and Cell Biology, Agency of Science, Technology and Research (A-Star), Singapore
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Tomasz K Prajsnar
1Department of Infection, Immunity and Cardiovascular disease, Medical School, University of Sheffield, S10 2TN, UK
2The Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK
4Institute Biology Leiden, Leiden University, Leiden, The Netherlands
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Justyna J Serba
1Department of Infection, Immunity and Cardiovascular disease, Medical School, University of Sheffield, S10 2TN, UK
2The Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK
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Rebecca D Tonge
5Sheffield institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, S10 2HQ, UK
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Andrew J Grierson
2The Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK
5Sheffield institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, S10 2HQ, UK
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Philip W Ingham
3Institute of Molecular and Cell Biology, Agency of Science, Technology and Research (A-Star), Singapore
6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
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Stephen A Renshaw
1Department of Infection, Immunity and Cardiovascular disease, Medical School, University of Sheffield, S10 2TN, UK
2The Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK
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Simon A Johnston
1Department of Infection, Immunity and Cardiovascular disease, Medical School, University of Sheffield, S10 2TN, UK
2The Bateson Centre, University of Sheffield, Sheffield, S10 2TN, UK
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  • For correspondence: s.a.johnston@sheffield.ac.uk
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Abstract

Autophagy leads to degradation of cellular components, and has an important role in destroying intracellular pathogens. Autophagy receptors, including p62, target invading intracellular pathogens to the autophagy pathway for degradation. p62 is able to co-localise with intracellular Staphylococcus aureus, previously shown in vitro, however, whether p62 is beneficial or detrimental in host defence against S. aureus had not been determined.

The intracellular fate of S. aureus over time following phagocytosis by neutrophils had not previously been analysed in vivo, and is not readily possible in other in vivo models. Here we use the excellent imaging and genetic capabilities of the zebrafish to analyse the fate and location S. aureus within neutrophils throughout infection. This information adds context to the dynamic temporal recruitment of autophagy proteins Lc3 and p62, accomplished using transgenic reporter lines.

We demonstrate, using a new p62 zebrafish mutant to block host p62 function, that p62 is required for a favourable host outcome in the zebrafish S. aureus infection model. We examine the fate of S. aureus throughout the time-course of infection, including bacterial degradation and cellular location, and establish that Lc3 and p62 recruitment to S. aureus within the neutrophil is altered depending on bacterial location within the neutrophil. We suggest that in vivo Lc3 marking of bacterial phagosomes within neutrophils may lead to bacterial degradation and that p62 is important for controlling cytoplasmic bacteria.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 11, 2019.
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Neutrophils use selective autophagy receptor p62 to target Staphylococcus aureus for degradation in the zebrafish model
Josie F Gibson, Tomasz K Prajsnar, Justyna J Serba, Rebecca D Tonge, Andrew J Grierson, Philip W Ingham, Stephen A Renshaw, Simon A Johnston
bioRxiv 604884; doi: https://doi.org/10.1101/604884
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Neutrophils use selective autophagy receptor p62 to target Staphylococcus aureus for degradation in the zebrafish model
Josie F Gibson, Tomasz K Prajsnar, Justyna J Serba, Rebecca D Tonge, Andrew J Grierson, Philip W Ingham, Stephen A Renshaw, Simon A Johnston
bioRxiv 604884; doi: https://doi.org/10.1101/604884

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