title: Molecular analysis of asymptomatic bacteriuria Escherichia coli strain VR50 reveals adaptation to the urinary tract by gene acquisition.
abstract: Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia s.beatson@uq.edu.au m.schembri@uq.edu.au.
authors: Scott A
authors: SA
authors: Beatson
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Nouri L
authors: NL
authors: Ben Zakour
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Makrina
authors: M
authors: Totsika
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Brian M
authors: BM
authors: Forde
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Rebecca E
authors: RE
authors: Watts
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Amanda N
authors: AN
authors: Mabbett
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Jan M
authors: JM
authors: Szubert
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Sohinee
authors: S
authors: Sarkar
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Minh-Duy
authors: MD
authors: Phan
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Kate M
authors: KM
authors: Peters
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Nicola K
authors: NK
authors: Petty
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Nabil-Fareed
authors: NF
authors: Alikhan
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Mitchell J
authors: MJ
authors: Sullivan
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Jayde A
authors: JA
authors: Gawthorne
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Mitchell
authors: M
authors: Stanton-Cook
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
authors: Nguyen Thi Khanh
authors: NT
authors: Nhu
authors: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Teik Min
authors: TM
authors: Chong
authors: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Wai-Fong
authors: WF
authors: Yin
authors: Division of Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Kok-Gan
authors: KG
authors: Chan
authors: Centre for Biological Sequence Analysis, DTU Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors: Viktoria
authors: V
authors: Hancock
authors: Centre for Biological Sequence Analysis, DTU Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors: David W
authors: DW
authors: Ussery
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia Griffith Health Institute and School of Medical Science, Griffith Health Centre, Griffith University, Gold Coast, Queensland, Australia.
authors: Glen C
authors: GC
authors: Ulett
authors: Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia s.beatson@uq.edu.au m.schembri@uq.edu.au.
authors: Mark A
authors: http://orcid.org/0000-0003-4863-9260
authors: MA
authors: Schembri
mesh_terms: D000220:Adaptation, Biological; D000328:Adult; D000818:Animals; D001422:Bacterial Adhesion; D001437:Bacteriuria / Q000382:microbiology*; D002353:Carrier State / Q000382:microbiology*; D002460:Cell Line; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology*; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial; D006801:Humans; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D014551:Urinary Tract / Q000382:microbiology*
chemical_list: D004269:DNA, Bacterial