Enteropathogenic Escherichia coli remodels host endosomes to promote endocytic turnover and breakdown of surface polarity
| العنوان: | Enteropathogenic Escherichia coli remodels host endosomes to promote endocytic turnover and breakdown of surface polarity |
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| المؤلفون: | Rachana Pattani Ramachandran, Michael Belenky, William Breuer, Naomi Melamed-Book, Lynne A. Lapierre, Benjamin Aroeti, Ritesh Ranjan Pal, Ilan Rosenshine, Efrat Zlotkin-Rivkin, Gil Friedman, Ephrem G. Kassa, James R. Goldenring, Aryeh Weiss, Dana Reichmann |
| المصدر: | PLoS Pathogens, Vol 15, Iss 6, p e1007851 (2019) PLoS Pathogens |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Confocal Microscopy, Cell Membranes, Endocytic cycle, Cultured tumor cells, Diagnostic Radiology, Enteropathogenic Escherichia coli, Spectrum Analysis Techniques, Medicine and Health Sciences, Biology (General), Escherichia coli Infections, Microscopy, 0303 health sciences, Secretory Pathway, biology, Chemistry, Radiology and Imaging, 030302 biochemistry & molecular biology, Infection Imaging, Light Microscopy, Flow Cytometry, Endocytosis, Cell biology, Transcytosis, Cell Processes, Spectrophotometry, Cell lines, Cytophotometry, Cellular Structures and Organelles, Biological cultures, Research Article, Imaging Techniques, Endosome, QH301-705.5, Immunology, Endosomes, Microbiology, Clathrin, EEA1, 03 medical and health sciences, Diagnostic Medicine, Virology, Genetics, Humans, Secretion, Vesicles, HeLa cells, Molecular Biology, 030304 developmental biology, Cell Membrane, Biology and Life Sciences, Membrane Proteins, Cell Biology, RC581-607, Cell cultures, Research and analysis methods, Membrane protein, biology.protein, Parasitology, Immunologic diseases. Allergy |
| الوصف: | Enteropathogenic E. coli (EPEC) is an extracellular diarrheagenic human pathogen which infects the apical plasma membrane of the small intestinal enterocytes. EPEC utilizes a type III secretion system to translocate bacterial effector proteins into its epithelial hosts. This activity, which subverts numerous signaling and membrane trafficking pathways in the infected cells, is thought to contribute to pathogen virulence. The molecular and cellular mechanisms underlying these events are not well understood. We investigated the mode by which EPEC effectors hijack endosomes to modulate endocytosis, recycling and transcytosis in epithelial host cells. To this end, we developed a flow cytometry-based assay and imaging techniques to track endosomal dynamics and membrane cargo trafficking in the infected cells. We show that type-III secreted components prompt the recruitment of clathrin (clathrin and AP2), early (Rab5a and EEA1) and recycling (Rab4a, Rab11a, Rab11b, FIP2, Myo5b) endocytic machineries to peripheral plasma membrane infection sites. Protein cargoes, e.g. transferrin receptors, β1 integrins and aquaporins, which exploit the endocytic pathways mediated by these machineries, were also found to be recruited to these sites. Moreover, the endosomes and cargo recruitment to infection sites correlated with an increase in cargo endocytic turnover (i.e. endocytosis and recycling) and transcytosis to the infected plasma membrane. The hijacking of endosomes and associated endocytic activities depended on the translocated EspF and Map effectors in non-polarized epithelial cells, and mostly on EspF in polarized epithelial cells. These data suggest a model whereby EPEC effectors hijack endosomal recycling mechanisms to mislocalize and concentrate host plasma membrane proteins in endosomes and in the apically infected plasma membrane. We hypothesize that these activities contribute to bacterial colonization and virulence. Author summary Enteropathogenic Escherichia coli (EPEC) are pathogenic bacteria that cause infantile diarrhea. Upon ingestion, EPEC reaches the small intestine, where an injection device termed the type III secretion system is utilized to inject a set of effector proteins from the bacteria into the host cell. These proteins manipulate the localization and functions of host proteins, lipids and organelles and contribute to the emergence of the EPEC disease. The molecular mechanisms underlying the functions of the EPEC effector proteins are not completely understood. Here we show that early upon infection, two such effector proteins, EspF and Map, hijack host endosomes at bacterial adherence sites to facilitate endocytosis and recycling of plasma membrane proteins at these sites. The consequence of this event is the enrichment and mislocalization of host plasma membrane proteins at infection sites. One such protein is the transferrin receptor, which is a carrier for transferrin, whose function is to mediate cellular uptake of iron. Iron is a critical nutrient for bacterial growth and survival. We postulate that the unique manipulation of transferrin receptor endocytic membrane trafficking by EPEC plays an important role in its survival on the luminal surface of the intestinal epithelium. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4cc5122845c0acccc9e3e0f28684569 https://doaj.org/article/0113612a3677415592436561aea27c2f |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c4cc5122845c0acccc9e3e0f28684569 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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