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      A requirement for septins and the autophagy receptor p62 in the proliferation of intracellular Shigella

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          Abstract

          Shigella flexneri, a Gram‐negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. During infection of epithelial cells, Shigella escape from the phagosome to the cytosol, where they reroute host cell glycolysis to obtain nutrients for proliferation. Septins, a poorly understood component of the cytoskeleton, can entrap cytosolic Shigella targeted to autophagy in cage‐like structures to restrict bacterial proliferation. Although bacterial entrapment by septin caging has been the subject of intense investigation, the role of septins and the autophagy machinery in the proliferation of noncaged Shigella is mostly unknown. Here, we found that intracellular Shigella fail to efficiently proliferate in SEPT2‐, SEPT7‐, or p62/SQSTM1‐depleted cells. Consistent with a failure to proliferate, single cell analysis of bacteria not entrapped in septin cages showed that the number of metabolically active Shigella in septin‐ or p62‐depleted cells is reduced. Targeted metabolomic analysis revealed that host cell glycolysis is dysregulated in septin‐depleted cells, suggesting a key role for septins in modulation of glycolysis. Together, these results suggest that septins and the autophagy machinery may regulate metabolic pathways that promote the proliferation of intracellular Shigella not entrapped in septin cages.

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          Most cited references 54

          • Record: found
          • Abstract: not found
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          Cleavage of structural proteins during the assembly of the head of bacteriophage T4.

           U K Laemmli (1970)
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            On the origin of cancer cells.

             O WARBURG (1956)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Escape of intracellular Shigella from autophagy.

              The degradation of undesirable cellular components or organelles, including invading microbes, by autophagy is crucial for cell survival. Here, Shigella, an invasive bacteria, was found to be able to escape autophagy by secreting IcsB by means of the type III secretion system. Mutant bacteria lacking IcsB were trapped by autophagy during multiplication within the host cells. IcsB did not directly inhibit autophagy. Rather, Shigella VirG, a protein required for intracellular actin-based motility, induced autophagy by binding to the autophagy protein, Atg5. In nonmutant Shigella, this binding is competitively inhibited by IcsB binding to VirG.
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                Author and article information

                Contributors
                g.larrouy-maumus@imperial.ac.uk
                s.mostowy@imperial.ac.uk
                Journal
                Cytoskeleton (Hoboken)
                Cytoskeleton (Hoboken)
                10.1002/(ISSN)1949-3592
                CM
                Cytoskeleton (Hoboken, N.j.)
                John Wiley and Sons Inc. (Hoboken )
                1949-3584
                1949-3592
                10 September 2018
                January 2019
                : 76
                : 1 , The Septin Cytoskeleton ( doiID: 10.1002/cm.v76.1 )
                : 163-172
                Affiliations
                [ 1 ] MRC Centre for Molecular Bacteriology and Infection, Department of Medicine Section of Microbiology, Imperial College London London United Kingdom
                [ 2 ] Department of Immunology and Infection London School of Hygiene and Tropical Medicine, Keppel Street London United Kingdom
                [ 3 ] MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences Imperial College London London United Kingdom
                Author notes
                [* ] Correspondence

                Gerald Larrouy‐Maumus, MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London, UK.

                Email: g.larrouy-maumus@ 123456imperial.ac.uk

                or

                Serge Mostowy, MRC Centre for Molecular Bacteriology and Infection, Department of Medicine, Section of Microbiology, Imperial College London, London, UK.

                Email: s.mostowy@ 123456imperial.ac.uk

                [†]

                Co‐senior author.

                Article
                CM21453
                10.1002/cm.21453
                6519264
                29752866
                © 2018 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                Counts
                Figures: 3, Tables: 0, Pages: 10, Words: 6318
                Product
                Funding
                Funded by: Marie Skłodowska‐Curie
                Award ID: H2020‐MSCA‐IF‐2016‐752022
                Funded by: eMdical Research Council
                Award ID: MR/J006874/1
                Funded by: Wellcome Trust Senior Research Fellowship
                Award ID: 206444/Z/17/Z
                Funded by: Wellcome Trust Research Career Development Fellowship
                Award ID: WT097411MA
                Funded by: Lister Institute of Preventive Medicine
                Categories
                Short Report
                Short Report
                Custom metadata
                2.0
                cm21453
                January 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:15.05.2019

                Cell biology

                shigella, autophagy, cytoskeleton, metabolism, septin

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