OHSU

Heffron Lab

overview

Salmonella is a gram negative bacterial pathogen that can infect diverse hosts including birds, reptiles and mammals. Salmonella typhimurium causes a self limiting gastroenteritis in humans whereas the closely related Salmonella typhi causes frequently fatal typhoid fever. The ability of Salmonella to survive within macrophages, professional phagocytes of the immune system, is a critical component of virulence. Salmonella not only survives within, but actually replicates within macrophages and eventually kills them; presumably after using them as vehicles for dissemination into the spleen and liver. Salmonella is also studied because it is a model pathogen without parallel for dissecting basic pathogenic processes. Salmonella is able to invade eukaryotic cells and can evade detection and destruction by the immune system - traits that are essential to most human pathogens. Further, an excellent murine model for studying Salmonella exists, allowing for the dissection of the complex interactions that occur between a pathogen and an intact mammalian immune system. Additionally, Salmonella is easily cultivated, is genetically tractable, and amenable to molecular biology manipulations. My primary interest is in the dissection of Salmonella virulence. As described in the references above we have identified regulatory networks required for systemic infection and are now dissecting individual genes that play a key role along the infectious pathway.

One of my hopes is that we will be able to alter Salmonella to deliver protective antigens to the host when and where we want them delivered. This will require removing many genes that make Salmonella too pathogenic, adding genes that re-direct the bacteria to specific tissues, and then adding a program telling the bacteria to make and release specific proteins once it arrives. My laboratory has always been interested in developing new technology that may assist in our goals. We have developed a method to identify bacterial proteins that have access to the class I MHC pathway as described in Ellefson above (see figure of contact between a Salmonella infected macrophage and a specific T cell hybridoma). These bacterial proteins will elicit the strongest T cell response and are the ones that we are engineering for vaccines.

in detail

srfA, srfB, srfC

srfA, srfB, and srfC. Click to enlarge.

Salmonella is a gram negative bacterial pathogen that can infect diverse hosts including birds, reptiles and mammals. Salmonella typhimurium causes a self limiting gastroenteritis in humans whereas the closely related Salmonella typhi causes frequently fatal typhoid fever. The ability of Salmonella to survive within macrophages, professional phagocytes of the immune system, is a critical component of virulence. Salmonella not only survives within, but actually replicates within macrophages and eventually kills them; presumably after using them as vehicles for dissemination into the spleen and liver. Salmonella is also studied because it is a model pathogen without parallel for dissecting basic pathogenic processes. Salmonella is able to invade eukaryotic cells and can evade detection and destruction by the immune system - traits that are essential to most human pathogens. Further, an excellent murine model for studying Salmonella exists, allowing for the dissection of the complex interactions that occur between a pathogen and an intact mammalian immune system. Additionally, Salmonella is easily cultivated, is genetically tractable, and amenable to molecular biology manipulations. My primary interest is in the dissection of Salmonella virulence. As described in the references above we have identified regulatory networks required for systemic infection and are now dissecting individual genes that play a key role along the infectious pathway.


contact between a Salmonella infected macrophage and a specific T cell hybridoma

Contact between a Salmonella infected macrophage and a specific T cell hybridoma

One of my hopes is that we will be able to alter Salmonella to deliver protective antigens to the host when and where we want them delivered. This will require removing many genes that make Salmonella too pathogenic, adding genes that re-direct the bacteria to specific tissues, and then adding a program telling the bacteria to make and release specific proteins once it arrives. My laboratory has always been interested in developing new technology that may assist in our goals. We have developed a method to identify bacterial proteins that have access to the class I MHC pathway as described in Ellefson above (see figure of contact between a Salmonella infected macrophage and a specific T cell hybridoma). These bacterial proteins will elicit the strongest T cell response and are the ones that we are engineering for vaccines.