Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-017-10445-4
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dc.titleTargeting Deficiencies in the TLR5 Mediated Vaginal Response to Treat Female Recurrent Urinary Tract Infection
dc.contributor.authorAli, A.S.M
dc.contributor.authorMowbray, C
dc.contributor.authorLanz, M
dc.contributor.authorStanton, A
dc.contributor.authorBowen, S
dc.contributor.authorVarley, C.L
dc.contributor.authorHilton, P
dc.contributor.authorBrown, K
dc.contributor.authorRobson, W
dc.contributor.authorSouthgate, J
dc.contributor.authorAldridge, P.D
dc.contributor.authorTyson-Capper, A
dc.contributor.authorAbraham, S
dc.contributor.authorPickard, R.S
dc.contributor.authorHall, J
dc.date.accessioned2020-10-20T10:25:28Z
dc.date.available2020-10-20T10:25:28Z
dc.date.issued2017
dc.identifier.citationAli, A.S.M, Mowbray, C, Lanz, M, Stanton, A, Bowen, S, Varley, C.L, Hilton, P, Brown, K, Robson, W, Southgate, J, Aldridge, P.D, Tyson-Capper, A, Abraham, S, Pickard, R.S, Hall, J (2017). Targeting Deficiencies in the TLR5 Mediated Vaginal Response to Treat Female Recurrent Urinary Tract Infection. Scientific Reports 7 (1) : 11039. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-017-10445-4
dc.identifier.issn2045-2322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/178583
dc.description.abstractThe identification of the host defence peptides as target effectors in the innate defence of the uro-genital tract creates new translational possibilities for immunomodulatory therapies, specifically vaginal therapies to treat women suffering from rUTI, particularly those carrying the TLR5-C1174T SNP. Urinary tract infections (UTIs) are a microbial disease reported worldwide. Women are particularly susceptible with many suffering debilitating recurrent (r) infections. Treatment is by antibiotics, but such therapy is linked to antibiotic resistance and re-infection. This study explored the innate protective mechanisms of the urogenital tract with the aim of boosting such defences therapeutically. Modelling UTIs in vitro, human vaginal and bladder epithelial cells were challenged with uropathogenic Escherichia coli (CFT073) and microbial PAMPs including flagellin, LPS and peptidoglycan. Flagellin functioning via the TLR5/NF?B pathway was identified as the key UPEC virulence factor causing a significant increase (P < 0.05) in the production of the host-defence peptide (HDP), BD2. BD2-depleted urine samples from bladder infected mice supported increased UPEC growth, strengthening the significance of the HDPs in protecting the urogenital tissues from infection. Clinically, vaginal-douche BD2 concentrations were reduced (p < 0.05) in women suffering rUTIs, compared to age-matched healthy controls with concentrations further decreased (p < 0.05) in a TLR5392Stop SNP rUTI subgroup. Topical vaginal estrogen treatment increased (p < 0.001) BD2 concentrations in all women, including those carrying the SNP. These data identify therapeutic and antibiotic sparing roles for vaginal immunomodulatory agents that specifically target HDP induction, facilitate bacterial killing and disrupt the UPEC infection cycle. © 2017 The Author(s).
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectbeta defensin
dc.subjectDEFB4A protein, human
dc.subjectTLR5 protein, human
dc.subjecttoll like receptor 5
dc.subjectadult
dc.subjectaged
dc.subjectanimal
dc.subjectbiological model
dc.subjectdisease model
dc.subjectepithelium cell
dc.subjectEscherichia coli infection
dc.subjectfemale
dc.subjectgrowth, development and aging
dc.subjecthuman
dc.subjectimmunology
dc.subjectinnate immunity
dc.subjectmetabolism
dc.subjectmicrobiology
dc.subjectmiddle aged
dc.subjectmouse
dc.subjectrecurrent disease
dc.subjecturinary tract infection
dc.subjecturopathogenic Escherichia coli
dc.subjectvagina
dc.subjectyoung adult
dc.subjectAdult
dc.subjectAged
dc.subjectAnimals
dc.subjectbeta-Defensins
dc.subjectDisease Models, Animal
dc.subjectEpithelial Cells
dc.subjectEscherichia coli Infections
dc.subjectFemale
dc.subjectHumans
dc.subjectImmunity, Innate
dc.subjectMice
dc.subjectMiddle Aged
dc.subjectModels, Biological
dc.subjectRecurrence
dc.subjectToll-Like Receptor 5
dc.subjectUrinary Tract Infections
dc.subjectUropathogenic Escherichia coli
dc.subjectVagina
dc.subjectYoung Adult
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1038/s41598-017-10445-4
dc.description.sourcetitleScientific Reports
dc.description.volume7
dc.description.issue1
dc.description.page11039
dc.published.statepublished
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