{"data":{"id":"10.6084/m9.figshare.3121861","type":"dois","attributes":{"doi":"10.6084/m9.figshare.3121861","prefix":"10.6084","suffix":"m9.figshare.3121861","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Bauckman, Kyle A.","nameType":"Personal","givenName":"Kyle A.","familyName":"Bauckman","affiliation":[],"nameIdentifiers":[]},{"name":"Mysorekar, Indira U.","nameType":"Personal","givenName":"Indira U.","familyName":"Mysorekar","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Ferritinophagy drives uropathogenic \u003ci\u003eEscherichia coli\u003c/i\u003e persistence in bladder epithelial cells"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2016,"subjects":[{"subject":"Medicine"},{"subject":"Microbiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"Molecular Biology"},{"subject":"Biotechnology"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"69999 Biological Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"19999 Mathematical Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Mathematics","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Mathematics","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cancer"},{"subject":"Inorganic Chemistry"},{"subject":"FOS: Chemical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Chemical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Hematology"},{"subject":"110309 Infectious Diseases","subjectScheme":"FOR"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Health sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"60506 Virology","subjectScheme":"FOR"}],"contributors":[],"dates":[{"date":"2016-03-22","dateType":"Created"},{"date":"2016-04-29","dateType":"Updated"},{"date":"2016","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15548627.2016.1160176","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["14250254 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Autophagy is a cellular recycling pathway, which in many cases, protects host cells from infections by degrading pathogens. However, uropathogenic \u003ci\u003eEscherichia coli\u003c/i\u003e (UPEC), the predominant cause of urinary tract infections (UTIs), persist within the urinary tract epithelium (urothelium) by forming reservoirs within autophagosomes. Iron is a critical nutrient for both host and pathogen, and regulation of iron availability is a key host defense against pathogens. Iron homeostasis depends on the shuttling of iron-bound ferritin to the lysosome for recycling, a process termed ferritinophagy (a form of selective autophagy). Here, we demonstrate for the first time that UPEC shuttles with ferritin-bound iron into the autophagosomal and lysosomal compartments within the urothelium. Iron overload in urothelial cells induces ferritinophagy in an NCOA4-dependent manner causing increased iron availability for UPEC, triggering bacterial overproliferation and host cell death. Addition of even moderate levels of iron is sufficient to increase and prolong bacterial burden. Furthermore, we show that lysosomal damage due to iron overload is the specific mechanism causing host cell death. Significantly, we demonstrate that host cell death and bacterial burden can be reversed by inhibition of autophagy or inhibition of iron-regulatory proteins, or chelation of iron. Together, our findings suggest that UPEC persist in host cells by taking advantage of ferritinophagy. Thus, modulation of iron levels in the bladder may provide a therapeutic avenue to controlling UPEC persistence, epithelial cell death, and recurrent UTIs.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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