Enteropathogenic Escherichia coli regulates host-cell mitochondrial morphology

Autor: Jennifer Lising Roxas, Shylaja Ramamurthy, Katie Cocchi, Ilga Rutins, Anusha Harishankar, Al Agellon, John Scott Wilbur, Gresa Sylejmani, Gayatri Vedantam, V.K. Viswanathan
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Gut Microbes, Vol 14, Iss 1 (2022)
Druh dokumentu: article
ISSN: 19490976
1949-0984
1949-0976
DOI: 10.1080/19490976.2022.2143224
Popis: 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.
Databáze: Directory of Open Access Journals
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