| Many Gram-negative bacteria utilize a dedicated molecular machine to inject virulence factors into the cytosol of host cells during infection. One such bacteria, Yersinia enterocolitica, utilize the type III secretion system to establish lymphadenitis and pertinonitis and yield typical symptoms of abdominal infections that require antibiotic treatment. Yersinia are thought to gain access to the underlying lymphatic tissues where they encounter host macrophages. At the end of this journey most bacteria are presumably killed by macrophages, an obstacle that a pathogen will need to overcome in order to elicit a successful infection. Clearly Yersiniae achieve this goal, given the fact that these microbes multiply within and colonize lymphoid tissues. Upon macrophage contact, Yersiniae activate the type III secretion machinery to inject a set of toxins into the eukaryotic cell. These toxins, named Yersinia outer proteins (Yops), interfere with host cellular processes such as actin polymerization and signal transduction cascades, thereby preventing phagocytosis and killing the macrophage. Work presented herein revealed several events of type III secretion systems during the infection of host cells that allow the delivery of Yop proteins to the extracellular milieu as well as into the host cells. Work also allowed the identification of several potential host signals that may trigger the specific protein export events by derepressing several regulators of the Yersinia type III system. Additionally, mutants of regulatory factors were analyzed to define distinct regulatory pathways of type III secretion during infection of host cells. |
