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dc.contributor.authorTotsika, M
dc.contributor.authorKostakioti, M
dc.contributor.authorHannan, TJ
dc.contributor.authorUpton, Mathew
dc.contributor.authorBeatson, SA
dc.contributor.authorJanetka, JW
dc.contributor.authorHultgren, SJ
dc.contributor.authorSchembri, MA
dc.date.accessioned2018-03-10T10:17:41Z
dc.date.available2018-03-10T10:17:41Z
dc.date.issued2013-09-15
dc.identifier.issn0022-1899
dc.identifier.issn1537-6613
dc.identifier.urihttp://hdl.handle.net/10026.1/11057
dc.description.abstract

BACKGROUND: Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent. METHODS: Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958. RESULTS: We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration failed to prevent E. coli EC958-mediated UTI. However, 1 oral dose of a small-molecular-weight compound that inhibits FimH, the type 1 fimbriae adhesin, significantly reduced bacterial colonization of the bladder and prevented acute UTI. Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by >1000-fold. CONCLUSIONS: In this study, we provide novel insight into the pathogenic mechanisms used by the globally disseminated E. coli ST131 clone during acute and chronic UTI and establish the potential of FimH inhibitors as an alternative treatment against multidrug-resistant E. coli.

dc.format.extent921-928
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoeng
dc.publisherOxford University Press (OUP)
dc.subjectE. coli ST131
dc.subjecturopathogenic E. coli
dc.subjecturinary tract infection
dc.subjectantibiotic resistance
dc.subjecttype 1 fimbriae
dc.subjectmannoside
dc.subjectbiofilm
dc.titleA FimH Inhibitor Prevents Acute Bladder Infection and Treats Chronic Cystitis Caused by Multidrug-Resistant Uropathogenic Escherichia coli ST131
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, N.I.H., Extramural
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000324510200008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue6
plymouth.volume208
plymouth.publication-statusPublished
plymouth.journalThe Journal of Infectious Diseases
dc.identifier.doi10.1093/infdis/jit245
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR)
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Researchers in ResearchFish submission
dc.publisher.placeUnited States
dc.identifier.eissn1537-6613
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1093/infdis/jit245
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review


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