Regulation and characterization of novel fimbriae in Salmonella enterica serovar Typhimurium.

• Applicant: Dr. Torsten Sterzenbach
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258454545

Salmonella spp. encode for a large set of adhesins, including up to 13 different chaperone-usher (CU) fimbriae. But although previous studies suggest that most of them are expressed in infection models and are important for persistence and pathogenicity, only type 1 fimbriae are readily expressed in vitro. Tight regulation and redundancy between different fimbrial adhesins limits the ability to study them. We could recently show that type 1 fimbriae and plasmid-encoded fimbriae are expressed in a hierarchical manner via the posttranscriptional regulator CsrA. Preliminary results show that a third fimbrial structure, Std fimbriae, is expressed in a mutant devoid of type 1 fimbriae and plasmid-encoded fimbriae. Work by us and others suggest that fimbrial regulation is deeply embedded into regulation of other virulence factors of Salmonella like invasion and motility. The global goal of this study is to obtain a better understanding of the regulation of CU fimbriae and to express and characterize additional CU-fimbriae. Furthermore I want to obtain a better un¬derstanding, how expression of CU fimbriae is integrated into the regulation of other virulence fac¬tors of Salmonella.Therefore I will pursue the following two specific aims. (1) We will determine the mechanism of coregulation between type 1 fimbriae, plasmid-encoded fimbriae and Std-fimbriae. Furthermore, we will integrate the effects on invasion and motility into the regulatory model. (2) We generated a mutant devoid of all operons predicted to encode for CU fimbriae. We will complement this mutant with single operons encoding for CU fimbriae. Novel successfully expressed CU fimbriae will be purified and their ligands will be determined by the use of glycan arrays. The strategy of generating strains expressing a single CU fimbrial structure allows us to study their role in adhesion and pathogenicity without interference by the presence of additional CU fimbriae.The data obtained in this study will provide a better understanding of the regulon of CU fimbriae and their interplay with other virulence factors of Salmonbella. The characterization of a larger sub¬set of CU fimbriae will provide novel insights, why Salmonella encodes for such a large repertoire of CU fimbriae and their role in the lifestyle of Salmonella.

• DFG Programme: Research Grants