Salmonellosis continues to be an important health concern in the United States and throughout the world.  Salmonella is a genus of rod-shaped, Gram-negative, non-spore forming, predominantly motile enterobacteria.  Some pathogenic species commonly grow in the intestines of chickens and other warm blooded animals, including humans.  Several factors allowing Salmonella to colonize the intestines of chickens have been identified, such as type 1 fimbriae (hair like projections that surround the cell).  To this end, we have devised a genetic strategy to identify small biologically-active cyclic peptides that would have the ability to inhibit type 1 fimbrial expression, which will reduce the number of organisms carried in the intestinal tract.  The primary structural protein of type 1 fimbriae is produced by the fimA gene.  The fimA gene requires fimZy to activate expression and to allow production of type 1 fimbriae.  We have created a fimA-lacZY reporter plasmid that allows us to monitor when fimA expression is shut down.  A library of plasmids that produce small random cyclic peptides has been introduced into the Salmonella strain the carries this system and we are examining colonies in which fimA-lacZ expression is shut off using Mac Conkey agar plates for screening.  Plasmids producing small cyclic peptides that inhibit expression and production of fimA will be identified, sequenced, and characterized in detail.  We anticipate identifying a number of small cyclic peptides that inhibit type 1 fimbrial expression and presumably colonization of chickens by Salmonella.