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.
Highlights
It has been recognized that bacteria in their natural milieu seldom grow as non-differentiated, single cell organisms
We sought to investigate whether two E. coli biofilm components, curli fimbriae and cellulose, provide a similar protection against innate immune defense mechanisms of the urinary tract
We put special emphasis on the interaction with the human antimicrobial peptide LL-37, which plays a crucial role in the protection against uropathogenic E. coli
Summary
It has been recognized that bacteria in their natural milieu seldom grow as non-differentiated, single cell organisms. Instead, they form multicellular communities, biofilms, showing coordinated behavior [1]. The extracellular matrix contributes to the development of higher-ordered three-dimensional structures that offer advantages to the bacteria, such as increased resistance to antimicrobial substances, mechanical forces and to nutrient depletion [3,4,5]. Uropathogenic E. coli forms biofilm-like structures on and inside host cells in the absence of a foreign body [7,8,9], and the ability to form biofilms has been related to persistence of bacteria in the urinary tract [10]
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