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Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37.

Kai-Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, Kádas L, Hedlund KO, Johansson J, Chapman MR, Jacobson SH, Römling U, Agerberth B, Brauner A - PLoS Pathog. (2010)

Bottom Line: Our results suggest that curli and cellulose exhibit differential and complementary functions.Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys.Thus, even relatively low concentrations of LL-37 inhibited curli-mediated biofilm formation in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT
Bacterial growth in multicellular communities, or biofilms, offers many potential advantages over single-cell growth, including resistance to antimicrobial factors. Here we describe the interaction between the biofilm-promoting components curli fimbriae and cellulose of uropathogenic E. coli and the endogenous antimicrobial defense in the urinary tract. We also demonstrate the impact of this interplay on the pathogenesis of urinary tract infections. Our results suggest that curli and cellulose exhibit differential and complementary functions. Both of these biofilm components were expressed by a high proportion of clinical E. coli isolates. Curli promoted adherence to epithelial cells and resistance against the human antimicrobial peptide LL-37, but also increased the induction of the proinflammatory cytokine IL-8. Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys. Interestingly, LL-37 inhibited curli formation by preventing the polymerization of the major curli subunit, CsgA. Thus, even relatively low concentrations of LL-37 inhibited curli-mediated biofilm formation in vitro. Taken together, our data demonstrate that biofilm components are involved in the pathogenesis of urinary tract infections by E. coli and can be a target of local immune defense mechanisms.

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LL-37 prevents formation of biofilm by E. coli in vitro.(A) Different concentrations of LL-37 and the control peptides sLL-37 and VIP were added to the curli-expressing mutant. (B) At 2.5 µM, LL-37 caused more than 80% reduction of biofilm production, whereas the same concentration of the control peptides gave a reduction of only ∼10%. Mean and standard deviation from data of two separate experiments in triplicates are shown. The difference between LL-37 versus sLL-37 or VIP at 2.5 µM was statistically significant (*** P = 0.001, t-test). Similar results were obtained for the wild-type strain expressing both curli and cellulose (data not shown).
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ppat-1001010-g006: LL-37 prevents formation of biofilm by E. coli in vitro.(A) Different concentrations of LL-37 and the control peptides sLL-37 and VIP were added to the curli-expressing mutant. (B) At 2.5 µM, LL-37 caused more than 80% reduction of biofilm production, whereas the same concentration of the control peptides gave a reduction of only ∼10%. Mean and standard deviation from data of two separate experiments in triplicates are shown. The difference between LL-37 versus sLL-37 or VIP at 2.5 µM was statistically significant (*** P = 0.001, t-test). Similar results were obtained for the wild-type strain expressing both curli and cellulose (data not shown).

Mentions: At concentrations below the IC50 for bacterial growth, LL-37 inhibited curli-mediated biofilm formation with a reduction of more than 80% at 2.5 µM for both the wild-type (data not shown) and the cellulose-negative E. coli strain (Figure 6). To investigate the specificity for the inhibitory capacity, sLL-37 and VIP were analyzed in the same assay. Our results showed that the same concentration of these peptides reduced biofilm formation by only 10%, which is a significantly lower reduction than the effect of LL-37 (P = 0.001, Figure 6B). This indicates a sequence-specific inhibition of curli-mediated biofilm by LL-37.


Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37.

Kai-Larsen Y, Lüthje P, Chromek M, Peters V, Wang X, Holm A, Kádas L, Hedlund KO, Johansson J, Chapman MR, Jacobson SH, Römling U, Agerberth B, Brauner A - PLoS Pathog. (2010)

LL-37 prevents formation of biofilm by E. coli in vitro.(A) Different concentrations of LL-37 and the control peptides sLL-37 and VIP were added to the curli-expressing mutant. (B) At 2.5 µM, LL-37 caused more than 80% reduction of biofilm production, whereas the same concentration of the control peptides gave a reduction of only ∼10%. Mean and standard deviation from data of two separate experiments in triplicates are shown. The difference between LL-37 versus sLL-37 or VIP at 2.5 µM was statistically significant (*** P = 0.001, t-test). Similar results were obtained for the wild-type strain expressing both curli and cellulose (data not shown).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908543&req=5

ppat-1001010-g006: LL-37 prevents formation of biofilm by E. coli in vitro.(A) Different concentrations of LL-37 and the control peptides sLL-37 and VIP were added to the curli-expressing mutant. (B) At 2.5 µM, LL-37 caused more than 80% reduction of biofilm production, whereas the same concentration of the control peptides gave a reduction of only ∼10%. Mean and standard deviation from data of two separate experiments in triplicates are shown. The difference between LL-37 versus sLL-37 or VIP at 2.5 µM was statistically significant (*** P = 0.001, t-test). Similar results were obtained for the wild-type strain expressing both curli and cellulose (data not shown).
Mentions: At concentrations below the IC50 for bacterial growth, LL-37 inhibited curli-mediated biofilm formation with a reduction of more than 80% at 2.5 µM for both the wild-type (data not shown) and the cellulose-negative E. coli strain (Figure 6). To investigate the specificity for the inhibitory capacity, sLL-37 and VIP were analyzed in the same assay. Our results showed that the same concentration of these peptides reduced biofilm formation by only 10%, which is a significantly lower reduction than the effect of LL-37 (P = 0.001, Figure 6B). This indicates a sequence-specific inhibition of curli-mediated biofilm by LL-37.

Bottom Line: Our results suggest that curli and cellulose exhibit differential and complementary functions.Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys.Thus, even relatively low concentrations of LL-37 inhibited curli-mediated biofilm formation in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT
Bacterial growth in multicellular communities, or biofilms, offers many potential advantages over single-cell growth, including resistance to antimicrobial factors. Here we describe the interaction between the biofilm-promoting components curli fimbriae and cellulose of uropathogenic E. coli and the endogenous antimicrobial defense in the urinary tract. We also demonstrate the impact of this interplay on the pathogenesis of urinary tract infections. Our results suggest that curli and cellulose exhibit differential and complementary functions. Both of these biofilm components were expressed by a high proportion of clinical E. coli isolates. Curli promoted adherence to epithelial cells and resistance against the human antimicrobial peptide LL-37, but also increased the induction of the proinflammatory cytokine IL-8. Cellulose production, on the other hand, reduced immune induction and hence delayed bacterial elimination from the kidneys. Interestingly, LL-37 inhibited curli formation by preventing the polymerization of the major curli subunit, CsgA. Thus, even relatively low concentrations of LL-37 inhibited curli-mediated biofilm formation in vitro. Taken together, our data demonstrate that biofilm components are involved in the pathogenesis of urinary tract infections by E. coli and can be a target of local immune defense mechanisms.

Show MeSH
Related in: MedlinePlus