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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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Cellulose delays bacterial elimination in vivo.(A) The expression of cellulose in curliated strains increased the number of bacteria in kidneys determined at 48 h p.i. (* P = 0.011, Mann-Whitney U test). The expression of curli in the absence of cellulose, on the other hand, mediated a more rapid elimination (# P = 0.011, Mann-Whitney U test). Individual values from n = 5–8 mice/group and medians are shown. (B) Cellulose expression reduces bacterial clearance by neutrophils. Control mice (Neu +) and mice with induced neutropenia (Neu −) were infected with curliated E. coli strains, and the bacterial load in the kidneys was determined 48 h p.i. A difference between bacteria with or without cellulose was only seen in the presence of neutrophils (P = 0.001, Mann-Whitney U test). Individual values from n = 9–12 mice/group and medians are shown.
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ppat-1001010-g003: Cellulose delays bacterial elimination in vivo.(A) The expression of cellulose in curliated strains increased the number of bacteria in kidneys determined at 48 h p.i. (* P = 0.011, Mann-Whitney U test). The expression of curli in the absence of cellulose, on the other hand, mediated a more rapid elimination (# P = 0.011, Mann-Whitney U test). Individual values from n = 5–8 mice/group and medians are shown. (B) Cellulose expression reduces bacterial clearance by neutrophils. Control mice (Neu +) and mice with induced neutropenia (Neu −) were infected with curliated E. coli strains, and the bacterial load in the kidneys was determined 48 h p.i. A difference between bacteria with or without cellulose was only seen in the presence of neutrophils (P = 0.001, Mann-Whitney U test). Individual values from n = 9–12 mice/group and medians are shown.

Mentions: In the initial stages of UTI, curli promoted colonization (Figure 2A+E). We further investigated the later course of UTI. Mice were infected with isogenic strains expressing curli and/or cellulose, and kidneys were analyzed 48 h post infection (p.i.). MIP-2 is the major neutrophil chemoattractant in the urinary tract [25]. Corresponding to immune induction (Figure 2F), the curliated mutant was more efficiently eliminated after 48 h p.i. than the wild-type strain with cellulose (P = 0.011, Figure 3A).


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)

Cellulose delays bacterial elimination in vivo.(A) The expression of cellulose in curliated strains increased the number of bacteria in kidneys determined at 48 h p.i. (* P = 0.011, Mann-Whitney U test). The expression of curli in the absence of cellulose, on the other hand, mediated a more rapid elimination (# P = 0.011, Mann-Whitney U test). Individual values from n = 5–8 mice/group and medians are shown. (B) Cellulose expression reduces bacterial clearance by neutrophils. Control mice (Neu +) and mice with induced neutropenia (Neu −) were infected with curliated E. coli strains, and the bacterial load in the kidneys was determined 48 h p.i. A difference between bacteria with or without cellulose was only seen in the presence of neutrophils (P = 0.001, Mann-Whitney U test). Individual values from n = 9–12 mice/group and medians are shown.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1001010-g003: Cellulose delays bacterial elimination in vivo.(A) The expression of cellulose in curliated strains increased the number of bacteria in kidneys determined at 48 h p.i. (* P = 0.011, Mann-Whitney U test). The expression of curli in the absence of cellulose, on the other hand, mediated a more rapid elimination (# P = 0.011, Mann-Whitney U test). Individual values from n = 5–8 mice/group and medians are shown. (B) Cellulose expression reduces bacterial clearance by neutrophils. Control mice (Neu +) and mice with induced neutropenia (Neu −) were infected with curliated E. coli strains, and the bacterial load in the kidneys was determined 48 h p.i. A difference between bacteria with or without cellulose was only seen in the presence of neutrophils (P = 0.001, Mann-Whitney U test). Individual values from n = 9–12 mice/group and medians are shown.
Mentions: In the initial stages of UTI, curli promoted colonization (Figure 2A+E). We further investigated the later course of UTI. Mice were infected with isogenic strains expressing curli and/or cellulose, and kidneys were analyzed 48 h post infection (p.i.). MIP-2 is the major neutrophil chemoattractant in the urinary tract [25]. Corresponding to immune induction (Figure 2F), the curliated mutant was more efficiently eliminated after 48 h p.i. than the wild-type strain with cellulose (P = 0.011, Figure 3A).

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