دورية أكاديمية
أعرض في EDS

Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist.

التفاصيل البيبلوغرافية
العنوان: Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist.
المؤلفون: Spaulding CN; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA., Klein RD; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA., Ruer S; Structural and Molecular Microbiology, VIB Center for Structural Biology, VIB, Pleinlaan 2, 1050 Brussels, Belgium.; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium., Kau AL; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA.; Department of Medicine, Washington University in St Louis, St Louis, Missouri 63110, USA., Schreiber HL; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA.; The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA., Cusumano ZT; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA., Dodson KW; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA., Pinkner JS; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA., Fremont DH; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Department of Pathology and Immunology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Department of Biochemistry and Molecular Biophysics, Washington University in St Louis, St Louis, Missouri 63110, USA., Janetka JW; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA.; Department of Biochemistry and Molecular Biophysics, Washington University in St Louis, St Louis, Missouri 63110, USA., Remaut H; Structural and Molecular Microbiology, VIB Center for Structural Biology, VIB, Pleinlaan 2, 1050 Brussels, Belgium.; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium., Gordon JI; Center for Genome Sciences and Systems Biology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Gut Microbiome and Nutrition Research, Washington University in St Louis, St Louis, Missouri 63110, USA., Hultgren SJ; Department of Molecular Microbiology, Washington University in St Louis, St Louis, Missouri 63110, USA.; Center for Women's Infectious Disease Research (CWIDR), Washington University in St Louis, St Louis, Missouri 63110, USA.
المصدر: Nature [Nature] 2017 Jun 22; Vol. 546 (7659), pp. 528-532. Date of Electronic Publication: 2017 Jun 14.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Fimbriae Proteins/*antagonists & inhibitors , Intestines/*drug effects , Intestines/*microbiology , Mannosides/*pharmacology , Phthalic Acids/*pharmacology , Urinary Tract Infections/*prevention & control , Uropathogenic Escherichia coli/*drug effects , Uropathogenic Escherichia coli/*isolation & purification, Adhesins, Escherichia coli/metabolism ; Amino Acid Sequence ; Animals ; Epithelial Cells/drug effects ; Epithelial Cells/microbiology ; Feces/microbiology ; Female ; Fimbriae Proteins/metabolism ; Fimbriae, Bacterial/classification ; Fimbriae, Bacterial/drug effects ; Fimbriae, Bacterial/genetics ; Fimbriae, Bacterial/metabolism ; Humans ; Intestines/cytology ; Mannosides/therapeutic use ; Mice ; Models, Molecular ; Phthalic Acids/therapeutic use ; Urinary Bladder/drug effects ; Urinary Bladder/microbiology ; Urinary Tract Infections/drug therapy ; Urinary Tract Infections/microbiology ; Uropathogenic Escherichia coli/classification ; Uropathogenic Escherichia coli/genetics
مستخلص: Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) affect 150 million people annually. Despite effective antibiotic therapy, 30-50% of patients experience recurrent UTIs. In addition, the growing prevalence of UPEC that are resistant to last-line antibiotic treatments, and more recently to carbapenems and colistin, make UTI a prime example of the antibiotic-resistance crisis and emphasize the need for new approaches to treat and prevent bacterial infections. UPEC strains establish reservoirs in the gut from which they are shed in the faeces, and can colonize the periurethral area or vagina and subsequently ascend through the urethra to the urinary tract, where they cause UTIs. UPEC isolates encode up to 16 distinct chaperone-usher pathway pili, and each pilus type may enable colonization of a habitat in the host or environment. For example, the type 1 pilus adhesin FimH binds mannose on the bladder surface, and mediates colonization of the bladder. However, little is known about the mechanisms underlying UPEC persistence in the gut. Here, using a mouse model, we show that F17-like and type 1 pili promote intestinal colonization and show distinct binding to epithelial cells distributed along colonic crypts. Phylogenomic and structural analyses reveal that F17-like pili are closely related to pilus types carried by intestinal pathogens, but are restricted to extra-intestinal pathogenic E. coli. Moreover, we show that targeting FimH with M4284, a high-affinity inhibitory mannoside, reduces intestinal colonization of genetically diverse UPEC isolates, while simultaneously treating UTI, without notably disrupting the structural configuration of the gut microbiota. By selectively depleting intestinal UPEC reservoirs, mannosides could markedly reduce the rate of UTIs and recurrent UTIs.
التعليقات: Comment in: Nature. 2017 Jun 22;546(7659):479-480. (PMID: 28614303)
Comment in: Nat Rev Urol. 2017 Aug;14(8):449. (PMID: 28631739)
Comment in: Nat Rev Microbiol. 2017 Aug;15(8):449. (PMID: 28669981)
Comment in: Nat Rev Nephrol. 2017 Sep;13(9):515. (PMID: 28713166)
Comment in: J Urol. 2018 Jan;199(1):30-31. (PMID: 29310190)
Comment in: J Urol. 2018 Jan;199(1):30-31. (PMID: 29310191)
Comment in: J Urol. 2018 Apr;199(4):874-875. (PMID: 29642325)
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معلومات مُعتمدة: R37 AI048689 United States AI NIAID NIH HHS; R01 AI048689 United States AI NIAID NIH HHS; R01 DK030292 United States DK NIDDK NIH HHS; P50 DK064540 United States DK NIDDK NIH HHS; R01 DK051406 United States DK NIDDK NIH HHS; F31 DK107057 United States DK NIDDK NIH HHS; K08 AI113184 United States AI NIAID NIH HHS; R37 DK030292 United States DK NIDDK NIH HHS; RC1 DK086378 United States DK NIDDK NIH HHS
المشرفين على المادة: 0 (Adhesins, Escherichia coli)
0 (M4284 compound)
0 (Mannosides)
0 (Phthalic Acids)
0 (fimH protein, E coli)
147680-16-8 (Fimbriae Proteins)
تواريخ الأحداث: Date Created: 20170615 Date Completed: 20171107 Latest Revision: 20220318
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC5654549
DOI: 10.1038/nature22972
PMID: 28614296
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/nature22972