Uropathogenic Escherichia coli Modulates Immune Responses and Its Curli Fimbriae Interact with the Antimicrobial Peptide LL-37

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.

Antimicrobial Resistance, Biofilm Formation, and Phylogenetic Grouping of Uropathogenic Escherichia coli Isolates in Egypt: The Role of Efflux Pump-Mediated Resistance

“…In the present study, in-vitro biofilm production was recorded in 76.5% of UPEC isolates; this is in contrast to other studies that showed different percentages of biofilm production among UPEC with 63.6%, 60.15%, and 51.9 % recorded in Egypt, India, and Nepal, respectively (15,40,41). Curli production was detected in 45.7% of the tested UPEC clinical isolates; a similar study from Sweden reported the detection of curli production among 54% of UPEC (42). A significant correlation was found between biofilm production and MDR phenotype among UPEC in the current study.…”

Genetic Analysis of the Role of yfiR in the Ability of Escherichia coli CFT073 To Control Cellular Cyclic Dimeric GMP Levels and To Persist in the Urinary Tract

“…Previous studies have shown that curli fibers produce an immune response by activating the host coagulation system and thus promoting an influx of white blood cells (34). However, curli fimbriae can also promote resistance to the host antimicrobial peptide LL-37 (36). Additional mutations in the yfiR deletion strain were therefore made to determine if the increased expression of curli fimbriae, or possibly even the increase in cellulose production, could be responsible for the attenuation of the yfiR deletion strain in vivo.…”

“…Various studies have demonstrated the ability of curli fimbriae to induce an immune response through Toll-like receptor 2 (TLR2) activation and generation of proinflammatory fibrinopeptides and by activating inducible nitric oxide synthase, a defense mechanism that produces large amounts of nitric oxide (33)(34)(35). Increased bacterial resistance to the antimicrobial peptide LL-37 in curli-fimbriated E. coli has also been demonstrated (36).…”

“…Transcription levels of the cellulose operons (bcsEFG and yhjRQbcsABZC) do not seem to be affected by c-di-GMP levels (16,20,31,(37)(38)(39). Production of cellulose in concert with curli fimbriae seems to dampen the immune response produced by the curli fibers (36). The coproduction of these factors also produces a distinctive in vitro plate phenotype termed the rdar morphotype, for the red, dry and rough colonies observed on agar plates that contain Congo red dye (29).…”

Innovative Solutions to Sticky Situations: Antiadhesive Strategies for Treating Bacterial Infections

“…A csgA mutant or csgB/csgG double mutant are both attenuated during acute infection in a murine model of cystitis, suggesting that curli fibers contribute to UTI pathogenesis (126). This defect in virulence could be partially explained by the binding of curli fibers with the human antimicrobial peptide LL-37 and the murine ortholog, cathelicidinrelated antimicrobial peptide (CRAMP) (127). This interaction is believed to sequester these peptides and attenuate their antimicrobial activity.…”