Secreted Effectors From Shigella flexneri That Target the Ubiquitin Proteasome System.

Shigella spp. is a food and water-borne pathogen and is the causative agent of dysentery, a severe diarrheal disease, which kills a million people yearly. Most of these victims are children under the age of 5 in the developing world. Our understanding of how Shigella spp. causes disease is limited and as a result, there is currently no effective vaccine against Shigella infection. The Shigella bacterium injects more than 20 proteins into the infected mammalian cells. These proteins, known as effectors, interfere with the immune response and are required for Shigella to cause disease. Recently, we have discovered the function of the largest class of these effector proteins, the IpaH proteins. IpaH proteins are a new class of enzymes that mark human proteins for destruction using the host cell's own machinery. By determining what human proteins the IpaH enzymes target we will learn what proteins are impaired by Shigella in order for it to cause disease. A basic understanding of how the IpaHs work will also aid in our understanding of Shigella pathogenesis and provide insight to novel therapies to treat dysentery.