Virulence and immunity in Rhodococcus equi

点击翻译按钮获取中文摘要

Rhodococcus equi is an important cause of a serious bacterial pneumonia in foals that can live inside the main phagocytic cell in their lungs.  It is really surprising that such a hostile environment allows this bacterium to survive, but it has some genes on a unique genetic structure, a "pathogenicity island", that allow it to do so. Our interest in this bacterial infection is not only that it causes economic loss and demoralization on horse-breeding farms around the world but also that it is related to Mycobacterium tuberculosis, the agent of human tuberculosis that infects over one-third of the human population.  This makes this organism of great comparative medical interest, since we may be able to use it to model aspects of tuberculosis in humans, for example testing novel antibacterial treatments. The work we are doing is designed to understand at a very detailed molecular level exactly how this bacterium is able to interfere with normal killing by phagocytic cells, especially what signals tells the bacterium that it is inside a phagocyte and how it then switches on proteins that it needs to survive in this usually hostile environment and switches off the proteins that it no longer needs. We are particularly interested in the role of iron and magnesium in controlling these switches, as well as in how the "pathogenicity island" interacts or "talks" to the genome, and vice versa. We will use many advanced techniques to study this, including inactivation of different genes. We will test many inactivated genes to see if they reduce the ability of this bacterium now to cause disease, and will find out whether we can use one or more of these mutants to immunize young foals by mouth, so that we can safely stop this awful disease.