Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology
ABSTRACTThe diarrheagenic pathogen enteropathogenic Escherichia coli is responsible for significant childhood mortality and morbidity. EPEC and related attaching-and-effacing (A/E) pathogens use a type III secretion system to hierarchically deliver effector proteins into host cells and manipulate ep...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2143224 |
| _version_ | 1811301162901569536 |
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| author | Jennifer Lising Roxas Shylaja Ramamurthy Katie Cocchi Ilga Rutins Anusha Harishankar Al Agellon John Scott Wilbur Gresa Sylejmani Gayatri Vedantam V.K. Viswanathan |
| author_facet | Jennifer Lising Roxas Shylaja Ramamurthy Katie Cocchi Ilga Rutins Anusha Harishankar Al Agellon John Scott Wilbur Gresa Sylejmani Gayatri Vedantam V.K. Viswanathan |
| author_sort | Jennifer Lising Roxas |
| collection | DOAJ |
| description | ABSTRACTThe diarrheagenic pathogen enteropathogenic Escherichia coli is responsible for significant childhood mortality and morbidity. EPEC and related attaching-and-effacing (A/E) pathogens use a type III secretion system to hierarchically deliver effector proteins into host cells and manipulate epithelial structure and function. Subversion of host mitochondrial biology is a key aspect of A/E pathogen virulence strategy, but the mechanisms remain poorly defined. We demonstrate that the early-secreted effector EspZ and the late-secreted effector EspH have contrasting effects on host mitochondrial structure and function. EspZ interacts with FIS1, a protein that induces mitochondrial fragmentation and mitophagy. Infection of epithelial cells with either wildtype EPEC or an isogenic espZ deletion mutant (ΔespZ) robustly upregulated FIS1 abundance, but a marked increase in mitochondrial fragmentation and mitophagy was seen only in ΔespZ-infected cells. FIS1-depleted cells were protected against ΔespZ-induced fission, and EspZ-expressing transfected epithelial cells were protected against pharmacologically induced mitochondrial fission and membrane potential disruption. Thus, EspZ interacts with FIS1 and blocks mitochondrial fragmentation and mitophagy. In contrast to WT EPEC, ΔespH-infected epithelial cells had minimal FIS1 upregulation and exhibited hyperfused mitochondria. Consistent with the contrasting impacts on organelle shape, mitochondrial membrane potential was preserved in ΔespH-infected cells, but profoundly disrupted in ΔespZ-infected cells. Collectively, our studies reveal hitherto unappreciated roles for two essential EPEC virulence factors in the temporal and dynamic regulation of host mitochondrial biology. |
| first_indexed | 2024-04-13T07:04:00Z |
| format | Article |
| id | doaj.art-0c6d3fffd716457f90989d266c83897c |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-13T07:04:00Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-0c6d3fffd716457f90989d266c83897c2022-12-22T02:57:03ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2143224Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphologyJennifer Lising Roxas0Shylaja Ramamurthy1Katie Cocchi2Ilga Rutins3Anusha Harishankar4Al Agellon5John Scott Wilbur6Gresa Sylejmani7Gayatri Vedantam8V.K. Viswanathan9School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USAABSTRACTThe diarrheagenic pathogen enteropathogenic Escherichia coli is responsible for significant childhood mortality and morbidity. EPEC and related attaching-and-effacing (A/E) pathogens use a type III secretion system to hierarchically deliver effector proteins into host cells and manipulate epithelial structure and function. Subversion of host mitochondrial biology is a key aspect of A/E pathogen virulence strategy, but the mechanisms remain poorly defined. We demonstrate that the early-secreted effector EspZ and the late-secreted effector EspH have contrasting effects on host mitochondrial structure and function. EspZ interacts with FIS1, a protein that induces mitochondrial fragmentation and mitophagy. Infection of epithelial cells with either wildtype EPEC or an isogenic espZ deletion mutant (ΔespZ) robustly upregulated FIS1 abundance, but a marked increase in mitochondrial fragmentation and mitophagy was seen only in ΔespZ-infected cells. FIS1-depleted cells were protected against ΔespZ-induced fission, and EspZ-expressing transfected epithelial cells were protected against pharmacologically induced mitochondrial fission and membrane potential disruption. Thus, EspZ interacts with FIS1 and blocks mitochondrial fragmentation and mitophagy. In contrast to WT EPEC, ΔespH-infected epithelial cells had minimal FIS1 upregulation and exhibited hyperfused mitochondria. Consistent with the contrasting impacts on organelle shape, mitochondrial membrane potential was preserved in ΔespH-infected cells, but profoundly disrupted in ΔespZ-infected cells. Collectively, our studies reveal hitherto unappreciated roles for two essential EPEC virulence factors in the temporal and dynamic regulation of host mitochondrial biology.https://www.tandfonline.com/doi/10.1080/19490976.2022.2143224Enteropathogenic Escherichia coliEPECEspZEspHFIS1mitophagy |
| spellingShingle | Jennifer Lising Roxas Shylaja Ramamurthy Katie Cocchi Ilga Rutins Anusha Harishankar Al Agellon John Scott Wilbur Gresa Sylejmani Gayatri Vedantam V.K. Viswanathan Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology Gut Microbes Enteropathogenic Escherichia coli EPEC EspZ EspH FIS1 mitophagy |
| title | Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology |
| title_full | Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology |
| title_fullStr | Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology |
| title_full_unstemmed | Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology |
| title_short | Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology |
| title_sort | enteropathogenic escherichia coli regulates host cell mitochondrial morphology |
| topic | Enteropathogenic Escherichia coli EPEC EspZ EspH FIS1 mitophagy |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2143224 |
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