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.
Most infections of the urinary tract are caused by uropathogenic E. coli. On abiotic surfaces, these bacteria are able to form biofilms, which protect them from various adverse environmental conditions. In this study, 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. We demonstrate that curli expression specifically reduces bacterial sensitivity to LL-37 by binding the peptide before reaching the bacterial cell membrane and exhibiting its bactericidal activity. A more general protection is mediated by cellulose, possibly by hiding immunogenic surface structures of the bacterium. In addition to providing protection, curli are also targeted by the immune system. The formation of new curli fibers is inhibited in the presence of LL-37. Moreover, curliated bacteria show higher immunogenicity than their non-curliated counterparts. Cellulose expression, on the other hand, appears to impair initial host colonization. In conclusion, our findings demonstrate an example of the tight interplay between bacterial virulence factors and the host immune defense.