The Functional Amyloid Curli Protects Escherichia coli against Complement-Mediated Bactericidal Activity

Area of Science:

• Microbiology
• Immunology
• Bacterial Pathogenesis

Background:

• Escherichia coli strains can be pathogenic, causing diseases like bacteremia and sepsis.
• Pathogenic E. coli often express virulence factors, such as curli, to resist host immune responses like the complement system.
• Curli, a bacterial amyloid, is involved in adherence and biofilm formation.

Purpose of the Study:

• To investigate the role of curli in E. coli survival during a human complement response.
• To determine how curli production affects E. coli's interaction with the complement system, particularly the classical and alternative pathways.

Main Methods:

• In vivo murine model of bacteremia to assess E. coli survival.
• In vitro assays using human serum to evaluate bacterial survival.
• Blocking experiments targeting the classical and alternative complement pathways.
• Analysis of bacterial binding to complement components C1q and C3b.

Main Results:

• Curli production significantly enhanced E. coli survival in a murine bacteremia model and in human serum.
• Curli was found to inhibit the classical complement pathway, a major contributor to complement activation.
• Curli did not appear to protect E. coli against alternative pathway complement activation.
• Curli increased the binding of E. coli to complement component C1q but not C3b.

Conclusions:

• Curli acts as a virulence factor that defends E. coli against complement-mediated killing.
• The protective effect of curli is primarily mediated through the inhibition of the classical complement pathway.
• Understanding curli's role in immune evasion is crucial for developing strategies against pathogenic E. coli infections.