Cargando…

Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the primary cause of community-acquired urinary tract infections (UTIs). UPEC bind the bladder using type 1 pili, encoded by the fim operon in nearly all E. coli. Assembled type 1 pili terminate in the FimH adhesin, which specifically binds to mannosylated gl...

Descripción completa

Detalles Bibliográficos
Autores principales: Greene, Sarah E., Hibbing, Michael E., Janetka, James, Chen, Swaine L., Hultgren, Scott J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488945/
https://www.ncbi.nlm.nih.gov/pubmed/26126855
http://dx.doi.org/10.1128/mBio.00820-15
_version_ 1782379258488815616
author Greene, Sarah E.
Hibbing, Michael E.
Janetka, James
Chen, Swaine L.
Hultgren, Scott J.
author_facet Greene, Sarah E.
Hibbing, Michael E.
Janetka, James
Chen, Swaine L.
Hultgren, Scott J.
author_sort Greene, Sarah E.
collection PubMed
description Uropathogenic Escherichia coli (UPEC) is the primary cause of community-acquired urinary tract infections (UTIs). UPEC bind the bladder using type 1 pili, encoded by the fim operon in nearly all E. coli. Assembled type 1 pili terminate in the FimH adhesin, which specifically binds to mannosylated glycoproteins on the bladder epithelium. Expression of type 1 pili is regulated in part by phase-variable inversion of the genomic element containing the fimS promoter, resulting in phase ON (expressing) and OFF (nonexpressing) orientations. Type 1 pili are essential for virulence in murine models of UTI; however, studies of urine samples from human UTI patients demonstrate variable expression of type 1 pili. We provide insight into this paradox by showing that human urine specifically inhibits both expression and function of type 1 pili. Growth in urine induces the fimS phase OFF orientation, preventing fim expression. Urine also contains inhibitors of FimH function, and this inhibition leads to a further bias in fimS orientation toward the phase OFF state. The dual effect of urine on fimS regulation and FimH binding presents a potential barrier to type 1 pilus-mediated colonization and invasion of the bladder epithelium. However, FimH-mediated attachment to human bladder cells during growth in urine reverses these effects such that fim expression remains ON and/or turns ON. Interestingly, FimH inhibitors called mannosides also induce the fimS phase OFF orientation. Thus, the transduction of FimH protein attachment or inhibition into epigenetic regulation of type 1 pilus expression has important implications for the development of therapeutics targeting FimH function.
format Online
Article
Text
id pubmed-4488945
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher American Society of Microbiology
record_format MEDLINE/PubMed
spelling pubmed-44889452015-07-07 Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli Greene, Sarah E. Hibbing, Michael E. Janetka, James Chen, Swaine L. Hultgren, Scott J. mBio Research Article Uropathogenic Escherichia coli (UPEC) is the primary cause of community-acquired urinary tract infections (UTIs). UPEC bind the bladder using type 1 pili, encoded by the fim operon in nearly all E. coli. Assembled type 1 pili terminate in the FimH adhesin, which specifically binds to mannosylated glycoproteins on the bladder epithelium. Expression of type 1 pili is regulated in part by phase-variable inversion of the genomic element containing the fimS promoter, resulting in phase ON (expressing) and OFF (nonexpressing) orientations. Type 1 pili are essential for virulence in murine models of UTI; however, studies of urine samples from human UTI patients demonstrate variable expression of type 1 pili. We provide insight into this paradox by showing that human urine specifically inhibits both expression and function of type 1 pili. Growth in urine induces the fimS phase OFF orientation, preventing fim expression. Urine also contains inhibitors of FimH function, and this inhibition leads to a further bias in fimS orientation toward the phase OFF state. The dual effect of urine on fimS regulation and FimH binding presents a potential barrier to type 1 pilus-mediated colonization and invasion of the bladder epithelium. However, FimH-mediated attachment to human bladder cells during growth in urine reverses these effects such that fim expression remains ON and/or turns ON. Interestingly, FimH inhibitors called mannosides also induce the fimS phase OFF orientation. Thus, the transduction of FimH protein attachment or inhibition into epigenetic regulation of type 1 pilus expression has important implications for the development of therapeutics targeting FimH function. American Society of Microbiology 2015-06-30 /pmc/articles/PMC4488945/ /pubmed/26126855 http://dx.doi.org/10.1128/mBio.00820-15 Text en Copyright © 2015 Greene et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Greene, Sarah E.
Hibbing, Michael E.
Janetka, James
Chen, Swaine L.
Hultgren, Scott J.
Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli
title Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli
title_full Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli
title_fullStr Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli
title_full_unstemmed Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli
title_short Human Urine Decreases Function and Expression of Type 1 Pili in Uropathogenic Escherichia coli
title_sort human urine decreases function and expression of type 1 pili in uropathogenic escherichia coli
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488945/
https://www.ncbi.nlm.nih.gov/pubmed/26126855
http://dx.doi.org/10.1128/mBio.00820-15
work_keys_str_mv AT greenesarahe humanurinedecreasesfunctionandexpressionoftype1piliinuropathogenicescherichiacoli
AT hibbingmichaele humanurinedecreasesfunctionandexpressionoftype1piliinuropathogenicescherichiacoli
AT janetkajames humanurinedecreasesfunctionandexpressionoftype1piliinuropathogenicescherichiacoli
AT chenswainel humanurinedecreasesfunctionandexpressionoftype1piliinuropathogenicescherichiacoli
AT hultgrenscottj humanurinedecreasesfunctionandexpressionoftype1piliinuropathogenicescherichiacoli