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Volume 191, Issue 2, Pages (February 2014)

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Presentation on theme: "Volume 191, Issue 2, Pages (February 2014)"— Presentation transcript:

1 Volume 191, Issue 2, Pages 519-528 (February 2014)
Rare Emergence of Symptoms during Long-Term Asymptomatic Escherichia coli Carriage without an Altered Virulence Factor Repertoire  Béla Köves, Ellaine Salvador, Jenny Grönberg-Hernández, Jaroslaw Zdziarski, Björn Wullt, Catharina Svanborg, Ulrich Dobrindt  The Journal of Urology  Volume 191, Issue 2, Pages (February 2014) DOI: /j.juro Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

2 Figure 1 Symptomatic UTI episodes during E. coli bacteriuria. A, mean ± SEM frequency (n) of symptomatic UTI episodes during year before inoculation and during year with E. coli bacteriuria in 20 patients (paired t-test). B, innate immune response of patients to symptomatic E. coli episodes quantified as urine cytokine and PMN levels. The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

3 Figure 2 Host response to ABU in vivo and in vitro. A, host response to symptomatic E. coli episodes. B, geometric mean ± SEM epithelial response to in vitro infection of A498 cells with E. coli wt, symptomatic E. coli re-isolates and uropathogenic E. coli strain CFT073 in 2 independent experiments. Fetal calf serum (FCS) (5%) was used to provide soluble CD14. The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

4 Figure 3 Virulence gene repertoire and characteristics of E. coli and symptomatic re-isolates. A, 1.6 kb plasmid and fim deletion were amplified by polymerase chain reaction (PCR) to verify E. coli identity in patient urine. B, identical virulence gene set was identified in E. coli and symptomatic re-isolates. C, E. coli and re-isolate phenotypic characteristics. The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

5 Figure 4 Phenotypic characterization of E. coli re-isolates from symptomatic episodes. A, adhesion to T-24 bladder epithelial cells and A498 kidney epithelial cells. B, biofilm formation in pooled human urine. C, growth kinetics in pooled human urine in vitro. D, motility on urine swarm agar plates. The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

6 Figure 5 Gene expression profiling of individual re-isolates. A, gene expression in re-isolates relative to E. coli Most regulated genes were unique to each isolate. B, hierarchical cluster analysis of deregulated genes in re-isolates relative to E. coli Strains were grown in vitro at 37C in pooled human urine. Values represent mean expression ratio of at least 3 independent microarray experiments. Green areas indicate significantly regulated (log twofold change, p <0.05) suppressed genes. Red areas indicate significantly regulated (log twofold change, p <0.050) up-regulated genes. Black areas indicate genes without statistically significant change (p >0.05). The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

7 Figure 6 Geometric mean ± SEM values of re-isolate virulence, as defined by in vivo infection (Mann-Whitney test). A, experimental infection of C3H/HeN mice by intravesical inoculation with 109 cfu in 0.1 ml E. coli or re-isolates from symptomatic episodes. Bacterial number in urine, kidneys and bladders, and neutrophil response revealed no difference in virulence (Mann-Whitney test). B, role of increased flagellation and motility were compared for E. coli wt and highly motile re-isolate Sp10. Mutant strains E. coli ΔfliC::cat and SN25, highly motile re-isolate from asymptomatic carrier, served as negative and positive control, respectively. Bacterial numbers in urine, kidneys and bladders, and neutrophil influx revealed no long-term advantage for flagellated strains. The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

8 Supplementary Figure 1 The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

9 Supplementary Figure 2 The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions

10 Supplementary Figure 3 The Journal of Urology  , DOI: ( /j.juro ) Copyright © 2014 American Urological Association Education and Research, Inc. Terms and Conditions


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