scholarly journals Identification and characterization of a phase-variable element that regulates the autotransporter UpaE in uropathogenicEscherichia coli

2018 ◽  
Author(s):  
E.J. Battaglioli ◽  
K.G.K Goh ◽  
T. S. Atruksang ◽  
K. Schwartz ◽  
M. A. Schembri ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Extracellular Matrix ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Reference Strain ◽  
Invertible Element ◽  
Matrix Proteins ◽  
Phase Variable ◽  
Third Phase ◽  
Strain Cft073

AbstractUropathogenicEscherichia coli(UPEC) are the most common etiological agent of uncomplicated urinary tract infection (UTI). An important mechanism of gene regulation in UPEC is phase variation that involves inversion of a promoter-containing DNA element via enzymatic activity of tyrosine recombinases, resulting in biphasic, ON or OFF expression of target genes. The UPEC reference strain CFT073 has five tyrosine site-specific recombinases that function at two previously characterized promoter inversion systems,fimSandhyxS. Three of the five recombinases are located proximally to their cognate target elements, which is typical of promoter inversion systems. The genes for the other two recombinases, IpuA and IpuB are located distal from these sites. Here, we identified and characterized a third phase variable invertible element in CFT073,ipuSlocated proximal toipuAandipuB. The inversion ofipuSis catalyzed by four of the five CFT073 recombinases. Orientation of the element drives transcription of a two-gene operon containingipuR, a predicted LuxR-type regulator, andupaE, a predicted autotransporter. We show that the predicted autotransporter UpaE is surface-located and facilitates biofilm formation as well as adhesion to extracellular matrix proteins in a K-12 recombinant background. Consistent with this phenotype, theipuSON condition in CFT073 results in defective swimming motility, increased adherence to human kidney epithelial cells, and a positive competitive kidney colonization advantage in experimental mouse UTI infections. Overall, the identification of a third phase-switch in UPEC that is regulated by a shared set of recombinases describes a complex phase-variable virulence network in UPEC.ImportanceUropathogenicEscherichia coli(UPEC) is the most common cause of urinary tract infection (UTI). ON versus OFF phase-switching by inversion of small DNA elements at two chromosome sites in UPEC regulates the expression of important virulence factors, including the type 1 fimbriae adhesion organelle. In this report, we describe a third invertible element,ipuS, in the UPEC reference strain CFT073. The inversion ofipuScontrols the phase variable expression ofupaE, an autotransporter gene that encodes a surface protein involved in adherence to extracellular matrix proteins and colonization of the kidneys in a murine model of UTI.

scholarly journals Identification and Characterization of a Phase-Variable Element That Regulates the Autotransporter UpaE in UropathogenicEscherichia coli

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
E. J. Battaglioli ◽  
K. G. K. Goh ◽  
T. S. Atruktsang ◽  
K. Schwartz ◽  
M. A. Schembri ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Extracellular Matrix ◽  
Urinary Tract Infection ◽  
Reference Strain ◽  
Invertible Element ◽  
Matrix Proteins ◽  
Phase Variable ◽  
Content Type ◽  
Third Phase ◽  
Strain Cft073

ABSTRACTUropathogenicEscherichia coli(UPEC) is the most common etiologic agent of uncomplicated urinary tract infection (UTI). An important mechanism of gene regulation in UPEC is phase variation that involves inversion of a promoter-containing DNA element via enzymatic activity of tyrosine recombinases, resulting in biphasic, ON or OFF expression of target genes. The UPEC reference strain CFT073 has five tyrosine site-specific recombinases that function at two previously characterized promoter inversion systems,fimSandhyxS. Three of the five recombinases are located proximally to their cognate target elements, which is typical of promoter inversion systems. The genes for the other two recombinases, IpuA and IpuB, are located distal from these sites. Here, we identified and characterized a third phase-variable invertible element in CFT073,ipuS, located proximal toipuAandipuB. The inversion ofipuSis catalyzed by four of the five CFT073 recombinases. Orientation of the element drives transcription of a two-gene operon containingipuR, a predicted LuxR-type regulator, andupaE, a predicted autotransporter. We show that the predicted autotransporter UpaE is surface located and facilitates biofilm formation as well as adhesion to extracellular matrix proteins in a K-12 recombinant background. Consistent with this phenotype, theipuSON condition in CFT073 results in defective swimming motility, increased adherence to human kidney epithelial cells, and a positive competitive kidney colonization advantage in experimental mouse UTIs. Overall, the identification of a third phase switch in UPEC that is regulated by a shared set of recombinases describes a complex phase-variable virulence network in UPEC.IMPORTANCEUropathogenicEscherichia coli(UPEC) is the most common cause of urinary tract infection (UTI). ON versus OFF phase switching by inversion of small DNA elements at two chromosome sites in UPEC regulates the expression of important virulence factors, including the type 1 fimbria adhesion organelle. In this report, we describe a third invertible element,ipuS, in the UPEC reference strain CFT073. The inversion ofipuScontrols the phase-variable expression ofupaE, an autotransporter gene that encodes a surface protein involved in adherence to extracellular matrix proteins and colonization of the kidneys in a murine model of UTI.

scholarly journals PhoU enhances the ability of extraintestinal pathogenic Escherichia coli strain CFT073 to colonize the murine urinary tract

Microbiology ◽  
2006 ◽  
Vol 152 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Eric L. Buckles ◽  
Xiaolin Wang ◽  
C. Virginia Lockatell ◽  
David E. Johnson ◽  
Michael S. Donnenberg
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Mutant Strain ◽  
Human Urine ◽  
Type Strain ◽  
Wild Type Strain ◽  
Wild Type ◽  
Strain Cft073

The phoU gene is the last cistron in the pstSCAB–phoU operon and functions as a negative regulator of the Pho regulon. The authors previously identified a phoU mutant of extraintestinal pathogenic Escherichia coli strain CFT073 and demonstrated that this mutant was attenuated for survival in the murine model of ascending urinary tract infection. It is hypothesized that the PhoU protein might serve as a urovirulence factor by indirectly affecting the expression of virulence-related genes. In this study, the phoU mutant was further characterized and PhoU was confirmed as a virulence factor. Western blot analysis demonstrated that insertion of the transposon in the phoU gene disrupted the expression of PhoU. The phoU mutant had derepressed alkaline phosphatase activity under phosphate-excess and -limiting conditions. In single-challenge murine ascending urinary tract infection experiments, quantitative cultures of urine, bladder and kidney revealed no significant differences between the phoU mutant strain and the wild-type strain CFT073. However, in competitive colonization experiments, the phoU mutant strain was significantly out-competed by the wild-type strain in the kidneys and urine and recovered in lower amount in the bladder. Complementation of the phoU mutant with a plasmid containing the wild-type phoU gene restored the expression of PhoU and alkaline phosphate activity to wild-type levels and no significant difference in colonization was observed between the phoU mutant containing the complementing plasmid and wild-type in competitive colonization experiments. In human urine, the phoU mutant and wild-type grew comparably when inoculated independently, indicating that the attenuation observed was not due to a general growth defect. However, as observed in vivo, the wild-type out-competed the phoU mutant in competition growth experiments in human urine. These data indicate that PhoU contributes to efficient colonization of the murine urinary tract and add PhoU to a short list of confirmed urovirulence factors.

scholarly journals Assessment of Virulence of Uropathogenic Escherichia coli Type 1 Fimbrial Mutants in Which the Invertible Element Is Phase-Locked On or Off

2002 ◽  
Vol 70 (7) ◽  
pp. 3344-3354 ◽  
Author(s):  
Nereus W. Gunther IV ◽  
Jennifer A. Snyder ◽  
Virginia Lockatell ◽  
Ian Blomfield ◽  
David E. Johnson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Invertible Element ◽  
Transcriptional Level ◽  
Wild Type ◽  
Invertible Elements ◽  
Tract Infections

ABSTRACT Type 1 fimbria is a proven virulence factor of uropathogenic Escherichia coli (UPEC), causing urinary tract infections. Expression of the fimbria is regulated at the transcriptional level by a promoter situated on an invertible element, which can exist in one of two different orientations. The orientation of the invertible element that allows the expression of type 1 fimbriae is defined as “on,” and the opposite orientation, in which no transcription occurs, is defined as “off.” During the course of a urinary tract infection, we have observed that the infecting E. coli population alternates between fimbriated and nonfimbriated states, with the fimbriated on orientation peaking at 24 h. We propose that the ability of the invertible element to switch orientations during infection is itself a virulence trait. To test this hypothesis, nucleotide sequence changes were introduced in the left inverted repeat of the invertible element of UPEC pyelonephritis strain CFT073 that locked the invertible elements permanently in either the on or the off orientation. The virulence of these mutants was assessed in the CBA mouse model of ascending urinary tract infection at 4, 24, 48, and 72 h postinoculation (hpi). We conducted independent challenges, in which bladders of mice were inoculated with either a single mutant or the wild type, and cochallenges, in which a mutant and the wild type were inoculated together to allow direct competition in the urinary tract. In both sets of experimental infections, the locked-off mutant was recovered from the urine, bladder, and kidneys in significantly lower numbers than the wild type at 24 hpi (P ≤ 0.05), demonstrating its attenuation. Conversely, the locked-on mutant was recovered in higher numbers than the wild type at 24 hpi (P ≤ 0.05), showing enhanced virulence of this mutant. No significant differences were seen between the mutants and wild type in the urine or the bladder at 48 or 72 hpi. However, the wild type outcompeted the locked-off mutant in the kidneys during the cochallenge experiment at 72 hpi (P = 0.009). Overall, these data suggest that the ability of the invertible element controlling type 1 fimbria expression to phase vary contributes significantly to virulence early (24 hpi) in the course of a urinary tract infection by UPEC and most profoundly influences colonization of the bladder.

scholarly journals Role of Phase Variation of Type 1 Fimbriae in a Uropathogenic Escherichia coli Cystitis Isolate during Urinary Tract Infection

2006 ◽  
Vol 74 (2) ◽  
pp. 1387-1393 ◽  
Author(s):  
Jennifer A. Snyder ◽  
Amanda L. Lloyd ◽  
C. Virginia Lockatell ◽  
David E. Johnson ◽  
Harry L. T. Mobley
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Invertible Element ◽  
Phase Variation ◽  
Type 1 Fimbriae ◽  
Constitutive Production

ABSTRACT Type 1 fimbrial phase-locked mutants of uropathogenic Escherichia coli cystitis isolate F11 were used to assess the role of the invertible element during urinary tract infection. Compared to the wild type, the phase-locked off mutant was attenuated, and constitutive production of type 1 fimbriae by the phase-locked on mutant did not provide a competitive advantage.

scholarly journals Escherichia coli bacteremia due to urinary tract infection complicated by acute myocarditis: A rare complication

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110236
Author(s):  
Mohamadanas Oudih ◽  
Thana Harhara
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Acute Myocarditis ◽  
Rare Complication ◽  
Kidney Injury ◽  
St Segment Elevation ◽  
Infection Treatment ◽  
St Segment

Acute myocarditis is a rare complication of Escherichia coli urinary tract infection and sepsis. We report the case of a previously healthy 55-year-old female who presented to our emergency department with diarrhea and hypotension. The basic metabolic panel results showed an increase in inflammatory markers and an acute kidney injury. Urine and blood cultures grew Escherichia coli. The patient subsequently developed sudden chest pain and shortness of breath, diffuse ST-segment elevation, and cardiac enzymes’ elevation. Coronary angiogram was normal, and transthoracic echocardiogram demonstrated normal ventricular functions. Cardiac magnetic resonance imaging was highly suspicious of myopericarditis. The patient made a full recovery after infection treatment with intravenous antibiotics, aspirin, and colchicine.

Molecular typing of Escherichia coli strains isolated from urinary tract infection by ERIC-PCR

Gene Reports ◽  
2021 ◽  
Vol 23 ◽  
pp. 101058
Author(s):  
Mahsa Movahedi ◽  
Omid Zarei ◽  
Maryam Hazhirkamal ◽  
Pezhman Karami ◽  
Leili Shokoohizadeh ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Molecular Typing
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