Shigella flexneri modulates stress granule composition and inhibits stress granule aggregation.
Invasion and multiplication of the facultative, cytosolic, enteropathogen Shigella flexneri within the colonic epithelial lining leads to an acute inflammatory response, fever and diarrhea. During the inflammatory process, infected cells are subjected to numerous stresses including heat, oxidative stress and genotoxic stress. The evolutionarily conserved pathway of cellular stress management is the formation of stress granules that store translationally inactive cellular mRNAs and interfere with cellular signalling pathways by sequestering signalling components. In this study, we investigated the ability of S. flexneri-infected cells to form stress granules in response to exogenous stresses. We found that S. flexneri infection inhibits movement of the stress granule markers eIF3 and eIF4B into stress granules and prevents the aggregation of G3BP1 and eIF4G-containing stress granules. This inhibition occurred only with invasive, but not with non-invasive bacteria and occurred in response to stresses that induce translational arrest through the phosphorylation of eIF2α and by treating cells with pateamine A, a drug that induces stress granules by inhibiting the eIF4A helicase. The S. flexneri-mediated stress granule inhibition could be largely phenocopied by the microtubule-destabilizing drug nocodazole and while S. flexneri infection did not lead to microtubule depolymerization, infection greatly enhanced acetylation of alpha-tubulin. Our data suggest that qualitative differences in the microtubule network or subversion of the microtubule-transport machinery by S. flexneri may be involved in preventing the full execution of this cellular stress response.
Unité de Pathogénie Microbienne Moléculaire (INSERM U786), France.
Pascale
P
Vonaesch
Unité de Pathogénie Microbienne Moléculaire (INSERM U786), France.
François-Xavier
FX
Campbell-Valois
Unité d'Analyse d'Images Biologiques, CNRS UMR 3691, Institut Pasteur, 25-28 Rue du Dr Roux, 75724, Paris Cedex 15, France.
Alexandre
0000-0002-9417-7389
A
Dufour
Unité de Pathogénie Microbienne Moléculaire (INSERM U786), France.|Microbiologie et Maladies Infectieuses, Collège de France, 11 Place Marcelin Berthelot, 75005, Paris, France.
Philippe J
PJ
Sansonetti
Unité de Pathogénie Microbienne Moléculaire (INSERM U786), France.
Pamela
P
Schnupf
D000199:Actins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004265:DNA Helicases; D004405:Dysentery, Bacillary / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004852:Epoxy Compounds / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism / Q000382:microbiology; D006367:HeLa Cells / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012763:Shigella flexneri / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D013312:Stress, Physiological / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology
D000199:Actins; D002352:Carrier Proteins; C000589329:EIF3B protein, human; D004852:Epoxy Compounds; D015852:Eukaryotic Initiation Factor-2; D039621:Eukaryotic Initiation Factor-3; D039642:Eukaryotic Initiation Factors; D018942:Macrolides; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D013844:Thiazoles; C031799:eIF-4B; C421324:pateamine A; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases