Fur Represses Adhesion to, Invasion of, and Intracellular Bacterial Community Formation within Bladder Epithelial Cells and Motility in Uropathogenic Escherichia coli

Kurabayashi, Kumiko; Agata, Tomohiro; Asano, Hirofumi; Tomita, Haruyoshi; Hirakawa, Hidetada

doi:10.1128/iai.00369-16

Cited by 42Escherichia coli research studiesBacterial Genetics and BiotechnologyUrinary Tract Infections Management

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Fur Represses Adhesion to, Invasion of, and Intracellular Bacterial Community Formation within Bladder Epithelial Cells and Motility in Uropathogenic Escherichia coli

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Kurabayashi, Kumiko, Agata, Tomohiro, Asano, Hirofumi, Tomita, Haruyoshi, Hirakawa, Hidetada·2016·Infection and Immunity

DOI 10.1128/iai.00369-16PMC PMC5067754

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Abstract

Uropathogenic Escherichia coli (UPEC) is a major pathogen that causes urinary tract infections (UTIs). This bacterium adheres to and invades the host cells in the bladder, where it forms biofilm-like polymicrobial structures termed intracellular bacterial communities (IBCs) that protect UPEC from antimicrobial agents and the host immune systems. Using genetic screening, we found that deletion of the fur gene, which encodes an iron-binding transcriptional repressor for iron uptake systems, elevated the expression of type I fimbriae and motility when UPEC was grown under iron-rich conditions, and it led to an increased number of UPEC cells adhering to and internalized in bladder epithelial cells. Consequently, the IBC colonies that the fur mutant formed in host cells were denser and larger than those formed by the wild-type parent strain. Fur is inactivated under iron-restricted conditions. When iron was depleted from the bacterial cultures, wild-type UPEC adhesion, invasion, and motility increased, similar to the case with the fur mutant. The purified Fur protein bound to regions upstream of fimA and flhD, which encode type I fimbriae and an activator of flagellar expression that contributes to motility, respectively. These results suggest that Fur is a repressor of fimA and flhD and that its repression is abolished under iron-depleted conditions. Based on our in vitro experiments, we conclude that UPEC adhesion, invasion, IBC formation, and motility are suppressed by Fur under iron-rich conditions but derepressed under iron-restricted conditions, such as in patients with UTIs.

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The fur mutant of UPEC has been demonstrated to be more virulent than wild-type strain.
“However, the fact that the fur mutant of UPEC has been demonstrated to be more virulent than the wild-type strain refutes this idea ( 32 ).”
From YdiV regulates Escherichia coli ferric uptake by manipulating the DNA-binding ability of Fur in a SlyD-dependent manner (2020) · cites this paper as [32]

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Additional file 1 of Functional characterization of Fur in iron metabolism, oxidative stress resistance and virulence of Riemerella anatipestifer
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Additional file 1 of Screening of antigenic epitopes related to the adhesion of the avian Escherichia coli Type 1 Fimbrial Agglutinin Domain
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Functional Genomic Studies of Uropathogenic Escherichia coli and Host Urothelial Cells when Intracellular Bacterial Communities Are Assembled*□S
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Authors: Kurabayashi, K., Agata, T., Asano, H., Tomita, H., & Hirakawa, H.
Affiliations: Gunma University (JP)
ORCID: Asano, Hirofumi
Tomita, Haruyoshi
Hirakawa, Hidetada
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2016-11
Volume: 84
Issue: 11
Pages: 3220-3231
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.00369-16
PMC: PMC5067754
OpenAlex: W2533390867
Cited by: 42
References: 40
Citations by year: 2026: 4 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 4 · 2017: 3
FWCI: 2.25
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: JSPS KAKENHI (25870115)
Topics: Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Health Sciences › Medicine › Urology › Urinary Tract Infections Management
Keywords: uropathogenic Escherichia coli, intracellular bacterial communities, bacterial adhesion, bacterial invasion, bacterial motility, type 1 fimbriae, fimA, flhD, iron regulation, iron limitation, bladder epithelial cells, urinary tract infection, biofilm formation, transcriptional repression
MeSH terms: Bacterial Adhesion, Bacterial Proteins, Urinary Bladder, Cell Movement, Epithelial Cells, Escherichia coli Infections, Humans, Iron, Fimbriae, Bacterial, Repressor Proteins, Gene Expression Regulation, Bacterial, Uropathogenic Escherichia coli

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Fur Represses Adhesion to, Invasion of, and Intracellular Bacterial Community Formation within Bladder Epithelial Cells and Motility in Uropathogenic Escherichia coli

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