title: Fur Represses Adhesion to, Invasion of, and Intracellular Bacterial Community Formation within Bladder Epithelial Cells and Motility in Uropathogenic Escherichia coli.
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.
authors: Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan.
authors: Kumiko
authors: K
authors: Kurabayashi
authors: Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan.
authors: Tomohiro
authors: T
authors: Agata
authors: Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan.
authors: Hirofumi
authors: H
authors: Asano
authors: Department of Bacteriology, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan.|Laboratory of Bacterial Drug Resistance, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan.
authors: Haruyoshi
authors: H
authors: Tomita
authors: Advanced Scientific Research Leaders Development Unit, Gunma University, Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan hirakawa@gunma-u.ac.jp.
authors: Hidetada
authors: H
authors: Hirakawa
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000382:microbiology*; D004927:Escherichia coli Infections / Q000382:microbiology*; D010861:Fimbriae, Bacterial / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D001743:Urinary Bladder / Q000382:microbiology*; D056689:Uropathogenic Escherichia coli / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D007501:Iron