Abstract
Uropathogenic Escherichia coli (UPEC) cause most uncomplicated urinary tract infections (UTIs) in humans. Because UTIs are considered to occur in an ascending manner, flagellum-mediated motility has been suggested to contribute to virulence by enabling UPEC to disseminate to the upper urinary tract. Previous studies from our laboratory and others have demonstrated a modest yet important role for flagella during ascending UTI. To better understand the role of flagella in vivo, we used biophotonic imaging to monitor UPEC infection and temporospatial flagellin gene expression during ascending UTI. Using em7-lux (constitutive) and fliC-lux transcriptional fusions, we show that flagellin expression by UPEC coincides with ascension of the ureters and colonization of the kidney. The patterns of fliC luminescence observed in vitro and in vivo were also validated by comparative quantitative PCR. Because fliC expression appeared coincident during ascension, we reassessed the contribution of fliC to ascending UTI using a low-dose intraurethral model of ascending UTI. Although wild-type UPEC were able to establish infection in the bladder and kidneys by 6 hours postinoculation, fliC mutant bacteria were able to colonize the bladder but were significantly attenuated in the kidneys at this early time point. By 48 hours postinoculation, the fliC mutant bacteria were attenuated in the bladder and kidneys and were not detectable in the spleen. These data provide compelling evidence that wild-type UPEC express flagellin and presumably utilize flagellum-mediated motility during UTI to ascend to the upper urinary tract and disseminate within the host.
MeSH Terms
Animals
Artificial Gene Fusion
Escherichia coli/genetics,pathogenicity
Escherichia coli Infections/microbiology
Escherichia coli Proteins/genetics
Flagella/genetics,physiology
Flagellin/genetics
Gene Expression
Genes, Reporter
Kidney/microbiology
Luciferases/analysis,genetics
Mice
Mice, Inbred Strains
Ureter/microbiology
Urinary Bladder/microbiology
Urinary Tract/microbiology
Urinary Tract Infections/microbiology
Chemicals
Escherichia coli Proteins
FliC protein, E coli
Flagellin
Luciferases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lane M Chelsea
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA.
Alteri Christopher J
Smith Sara N
Mobley Harry L T
References (28)
28 references, click to expand
-
Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains.
Infect Immun. 1990 May;58(5):1281-9
PMID: 2182540
-
Uropathogenicity in rats and mice of Providencia stuartii from long-term catheterized patients.
J Urol. 1987 Sep;138(3):632-5
PMID: 3625871
-
Extracellular replication of Listeria monocytogenes in the murine gall bladder.
Science. 2004 Feb 6;303(5659):851-3
PMID: 14764883
-
Evasion of Toll-like receptor 5 by flagellated bacteria.
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9247-52
PMID: 15956202
-
Reflux in the mouse model of urinary tract infection.
Infect Immun. 1998 Dec;66(12):6063-4
PMID: 9874598
-
Uropathogenic Escherichia coli flagella aid in efficient urinary tract colonization.
Infect Immun. 2005 Nov;73(11):7657-68
PMID: 16239570
-
Urinary tract infections.
Clin Obstet Gynecol. 1998 Sep;41(3):744-54
PMID: 9742370
-
Noninvasive biophotonic imaging for monitoring of catheter-associated urinary tract infections and therapy in mice.
Infect Immun. 2005 Jul;73(7):3878-87
PMID: 15972473
-
Transient interference with staphylococcal quorum sensing blocks abscess formation.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1691-6
PMID: 15665088
-
In vivo bioluminescence imaging for integrated studies of infection.
Cell Microbiol. 2004 Apr;6(4):303-17
PMID: 15009023
-
Role of motility in the colonization of uropathogenic Escherichia coli in the urinary tract.
Infect Immun. 2005 Nov;73(11):7644-56
PMID: 16239569
-
Dimorphic transition in Escherichia coli and Salmonella typhimurium: surface-induced differentiation into hyperflagellate swarmer cells.
Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8631-5
PMID: 8078935
-
Optimization of plasmid maintenance in the attenuated live vector vaccine strain Salmonella typhi CVD 908-htrA.
Infect Immun. 1999 Dec;67(12):6424-33
PMID: 10569759
-
The role of motility as a virulence factor in bacteria.
Int J Med Microbiol. 2002 Mar;291(8):605-14
PMID: 12008914
-
Roles for motility in bacterial-host interactions.
Mol Microbiol. 1997 Jun;24(6):1109-17
PMID: 9218761
-
Induction of urinary tract infection by intraurethral inoculation with Escherichia coli: refining the murine model.
J Infect Dis. 1995 Feb;171(2):462-5
PMID: 7844391
-
Microarray-based detection of Salmonella enterica serovar Typhimurium transposon mutants that cannot survive in macrophages and mice.
Infect Immun. 2005 Sep;73(9):5438-49
PMID: 16113260
-
In vivo, fliC expression by Salmonella enterica serovar Typhimurium is heterogeneous, regulated by ClpX, and anatomically restricted.
Mol Microbiol. 2006 Aug;61(3):795-809
PMID: 16803592
-
Cutting edge: Tlr5-/- mice are more susceptible to Escherichia coli urinary tract infection.
J Immunol. 2007 Apr 15;178(8):4717-20
PMID: 17404249
-
Selection for in vivo regulators of bacterial virulence.
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6889-94
PMID: 11391007
-
In vivo bioluminescence imaging of the murine pathogen Citrobacter rodentium.
Infect Immun. 2006 Sep;74(9):5391-6
PMID: 16926434
-
Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli.
Mol Microbiol. 2002 Feb;43(3):809-21
PMID: 11929534
-
Rapid direct method for monitoring antibiotics in a mouse model of bacterial biofilm infection.
Antimicrob Agents Chemother. 2003 Oct;47(10):3130-7
PMID: 14506020
-
Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria.
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12487-92
PMID: 16891416
-
Assessment of virulence of uropathogenic Escherichia coli type 1 fimbrial mutants in which the invertible element is phase-locked on or off.
Infect Immun. 2002 Jul;70(7):3344-54
PMID: 12065472
-
Transcriptome of uropathogenic Escherichia coli during urinary tract infection.
Infect Immun. 2004 Nov;72(11):6373-81
PMID: 15501767
-
Urinary tract infections.
Med Clin North Am. 1997 May;81(3):719-30
PMID: 9167654
-
Multiple control of flagellum biosynthesis in Escherichia coli: role of H-NS protein and the cyclic AMP-catabolite activator protein complex in transcription of the flhDC master operon.
J Bacteriol. 1999 Dec;181(24):7500-8
PMID: 10601207