Functional characterization of the periplasmic chaperone SurA and analysis of its role in the virulence of uropathogenic Escherichia coli

• Applicant: Privatdozentin Dr. Susanne Behrens-Kneip
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2008 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 80463314

The Escherichia coli periplasmic chaperone SurA for β-barrel outer membrane proteins plays a crucial role in outer membrane integrity and cell envelope homeostasis. In addition, SurA is required for full virulence of the uropathogenic E. coli (UPEC) cystitis strain UTI89. Lack of SurA interferes with the proper biogenesis of the adhesive type 1-fimbriae, an essential colonization determinant in cystitis. However, there is also evidence that the influence of this conserved chaperone on uropathogenicity is more complex. UPEC are a heterogeneous group of isolates that differ considerably in their repertoire and expression levels of virulence factors and cause urinary tract infections of varying severity and localization. By characterizing surA mutants of different UPEC isolates, including the wellstudied pyelonephritis strains E. coli 536 and CFT073, we have already identified additional virulence-associated traits that are affected by SurA. To gain a more complete understanding on how SurA contributes to UPEC virulence, we now seek to identify proteins relevant to disease causation that are affected by SurA using proteomic approaches complementary to further phenotype analysis as well as to examine the molecular basis of its pleiotropic effects. In addition, we will study the influence of SurA on the virulence potential of pyelonephritis-associated UPEC both in vitro and in vivo using cell culture and mouse infection models.

• DFG Programme: Research Grants