title: FNR regulates expression of important virulence factors contributing to pathogenicity of uropathogenic Escherichia coli.
abstract: Uropathogenic Escherichia coli (UPEC) is responsible for the majority of urinary tract infections (UTIs), which are some of the world's most common bacterial infections of humans. Here, we examined the role of FNR (fumarate and nitrate reduction), a well-known global regulator, in the pathogenesis of UPEC infections. We constructed an fnr deletion mutant of UPEC CFT073 and compared it to the wild type for changes in virulence, adherence, invasion, and expression of key virulence factors. Compared to the wild type, the fnr mutant was highly attenuated in the mouse model of human UTI and showed severe defects in adherence to and invasion of bladder and kidney epithelial cells. Our results showed that FNR regulates motility and multiple virulence factors, including expression of type I and P fimbriae, modulation of hemolysin expression, and expression of a novel pathogenicity island involved in α-ketoglutarate metabolism under anaerobic conditions. Our results demonstrate that FNR is a key global regulator of UPEC virulence and controls expression of important virulence factors that contribute to UPEC pathogenicity.
authors.affiliation: Departamento de Biofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Nicolle L
authors.initials: NL
authors.lastname: Barbieri
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Bryon
authors.initials: B
authors.lastname: Nicholson
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA Department of Avian and Rabbit Medicine, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Hussein
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Wentong
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Wannemuehler
authors.affiliation: Laboratory Animal Resources, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Dell'Anna
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Logue
authors.affiliation: Departamento de Biofísica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Horn
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Nolan
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA liganwu@iastate.edu.
authors.forename: Ganwu
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000382:microbiology; D004927:Escherichia coli Infections / Q000382:microbiology / Q000473:pathology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion; D008808:Mice, Inbred CBA; D014552:Urinary Tract Infections / Q000382:microbiology / Q000473:pathology; D056689:Uropathogenic Escherichia coli / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D007506:Iron-Sulfur Proteins; D037521:Virulence Factors