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Neutrophils use selective autophagy receptor Sqstm1/p62 to target Staphylococcus aureus for degradation in vivo in zebrafish.

Title: Neutrophils use selective autophagy receptor Sqstm1/p62 to target Staphylococcus aureus for degradation in vivo in zebrafish.
Authors: Gibson JF; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.; The Bateson Centre, University of Sheffield, Sheffield, UK.; Institute of Molecular and Cell Biology, Agency of Science, Technology and Research (A-star), Singapore.; Florey Institute, University of Sheffield, Sheffield, UK.; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.; Prajsnar TK; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.; The Bateson Centre, University of Sheffield, Sheffield, UK.; Institute Biology Leiden, Leiden University, Leiden, The Netherlands.; Hill CJ; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.; Tooke AK; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.; Serba JJ; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.; The Bateson Centre, University of Sheffield, Sheffield, UK.; Tonge RD; Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, UK.; Foster SJ; Florey Institute, University of Sheffield, Sheffield, UK.; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.; Grierson AJ; The Bateson Centre, University of Sheffield, Sheffield, UK.; Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, UK.; Ingham PW; Institute of Molecular and Cell Biology, Agency of Science, Technology and Research (A-star), Singapore.; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.; Renshaw SA; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.; The Bateson Centre, University of Sheffield, Sheffield, UK.; Florey Institute, University of Sheffield, Sheffield, UK.; Johnston SA; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK.; The Bateson Centre, University of Sheffield, Sheffield, UK.; Florey Institute, University of Sheffield, Sheffield, UK.
Source: Autophagy [Autophagy] 2021 Jun; Vol. 17 (6), pp. 1448-1457. Date of Electronic Publication: 2020 Jun 19.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101265188 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8635 (Electronic) Linking ISSN: 15548627 NLM ISO Abbreviation: Autophagy Subsets: MEDLINE
Imprint Name(s): Publication: 2015- : Philadelphia, PA : Taylor & Francis; Original Publication: Georgetown, TX : Landes Bioscience, 2005-
MeSH Terms: Autophagy/*physiology ; Neutrophils/*metabolism ; Sequestosome-1 Protein/*metabolism; Animals, Genetically Modified/metabolism ; Macrophages/metabolism ; Microtubule-Associated Proteins/metabolism ; Phagosomes/metabolism ; Zebrafish/metabolism ; Zebrafish Proteins/metabolism ; Animals ; Staphylococcus aureus
Abstract: Macroautophagy/autophagy functions to degrade cellular components and intracellular pathogens. Autophagy receptors, including SQSTM1/p62, target intracellular pathogens. Staphylococcus aureus is a significant pathogen of humans, especially in immunocompromise. S. aureus may use neutrophils as a proliferative niche, but their intracellular fate following phagocytosis has not been analyzed in vivo. In vitro, SQSTM1 can colocalize with intracellular Staphylococcus aureus, but whether SQSTM1 is beneficial or detrimental in host defense against S. aureus in vivo is unknown. Here we determine the fate and location of S. aureus within neutrophils throughout zebrafish infection. We show Lc3 and Sqstm1 recruitment to phagocytosed S. aureus is altered depending on the bacterial location within the neutrophil and that Lc3 marking of bacterial phagosomes within neutrophils may precede bacterial degradation. Finally, we show Sqstm1 is important for controlling cytosolic bacteria, demonstrating for the first time a key role of Sqstm1 in autophagic control of S. aureus in neutrophils.Abbreviations: AR: autophagy receptor; CFU: colony-forming unit; CHT: caudal hematopoietic tissue; GFP: green fluorescent protein; hpf: hours post-fertilization; hpi: hours post-infection; LWT: london wild-type: lyz: lysozyme; Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; RFP: red fluorescent protein; Sqstm1/p62: sequestosome 1; Tg: transgenic; TSA: tyramide signal amplification; UBD: ubiquitin binding domain.
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Grant Information: MR/M004864/1 United Kingdom MRC_ Medical Research Council; MR/N02995X/1 United Kingdom MRC_ Medical Research Council; MR/R001111/1 United Kingdom MRC_ Medical Research Council; MR/J009156/1 United Kingdom MRC_ Medical Research Council; G0700091 United Kingdom MRC_ Medical Research Council
Contributed Indexing: Keywords: Autophagy; bacterial infection; host-pathogen interactions; neutrophil; sqstm1/p62; staphylococcus aureus; xenophagy; zebrafish
Substance Nomenclature: 0 (Microtubule-Associated Proteins); 0 (Sequestosome-1 Protein); 0 (Zebrafish Proteins)
Entry Date(s): Date Created: 20200620 Date Completed: 20211230 Latest Revision: 20250530
Update Code: 20260130
PubMed Central ID: PMC8204994
DOI: 10.1080/15548627.2020.1765521
PMID: 32559122
Database: MEDLINE

Journal Article; Research Support, Non-U.S. Gov't