S. enterica serovar Typhimurium is an important human pathogen causing acute gastroenteritis following ingestion of contaminated food. One of the major vehicles of infection for humans is contaminated poultry because the bacteria easily infect these animals. In both hosts, humans and chickens, the pathogen colonizes and grows in the gastrointestinal (GI) tract. Very little is known about the microbiology of bacterial survival in this environment and one of the aims of this proposal is to investigate bacterial growth on intestinal epithelia of both humans and chickens. We have shown that a protein, FimZ, plays a crucial role in regulating the expression of several phenotypes that are involved in the host/pathogen interaction. This protein influences the ability of bacteria to move, adhere to, and invade eucaryotic cells. Each of these events is necessary for efficient colonization and growth. We propose to elucidate the mechanisms by which FimZ is produced and its ability to interact with other proteins. These will be important interactions since they will determine the level and degree of function of one of the major bacterial adherence proteins. In order to achieve these goals we propose to use techniques that will enable us to investigate the molecular pathogenies of salmonella organisms. The ability of serovar Typhimurium to colonize and grow on epithelial surfaces is a function of the production of adherence factors on the surface of the bacteria. These factors are frequently discrete appendages, named fimbriae or pili, that allow the bacteria to recognize receptors on eucaryotic cell surfaces. FimZ is a protein that regulates the expression of one of these adherence factors and our preliminary evidence indicates that there is coordinate interaction between fimbrial expression in serovar Typhimurium. These bacteria have the potential to produce numerous different types of fimbriae. It is currently unknown how the bacteria coordinate and integrate the expression of multiple fimbrial types. In this proposal we describe experiments to initiate studies on coordinate fimbrial gene expression. These will be the first systematic investigations of global fimbrial expression in serovar Typhimurium and will begin to address questions about the ability of these bacteria to non-stochastically produce adhesins in a programmed and regulated fashion. Since many pathogenic bacteria have the potential to produce multiple fimbrial types, these studies will also have significance for many species of pathogenic bacteria.
These studies investigate the coordinate regulation and role of Salmonella adherence factors. These factors are important in facilitating attachment to host cells as a first stage of infection.
| Zeiner, Sarah A; Dwyer, Brett E; Clegg, Steven (2013) FimY does not interfere with FimZ-FimW interaction during type 1 fimbria production by Salmonella enterica serovar Typhimurium. Infect Immun 81:4453-60 |
| Sterzenbach, Torsten; Nguyen, Kim T; Nuccio, Sean-Paul et al. (2013) A novel CsrA titration mechanism regulates fimbrial gene expression in Salmonella typhimurium. EMBO J 32:2872-83 |
| Zeiner, Sarah A; Dwyer, Brett E; Clegg, Steven (2012) FimA, FimF, and FimH are necessary for assembly of type 1 fimbriae on Salmonella enterica serovar Typhimurium. Infect Immun 80:3289-96 |
| Kisiela, Dagmara I; Kramer, Jeremy J; Tchesnokova, Veronika et al. (2011) Allosteric catch bond properties of the FimH adhesin from Salmonella enterica serovar Typhimurium. J Biol Chem 286:38136-47 |
| Clegg, Steven; Wilson, Janet; Johnson, Jeremiah (2011) More than one way to control hair growth: regulatory mechanisms in enterobacteria that affect fimbriae assembled by the chaperone/usher pathway. J Bacteriol 193:2081-8 |
