Hans Wolf-Watz
The Type III secretion system of pathogenic Yersinia
There are three human pathogenic strains of Yersinia; Y.pestis , Y.pseudotuberculosis and Y.enterocolitica . Y.pestis is the causative agent of plague; and was responsible for the Black death during the 14th century. This family of bacteria harbours a common virulence plasmid which encodes a number of secreted proteins collectively called Yops (Yersinia outer proteins)
These proteins are expressed during infection and they are major antihost factors. One of the main functions of the Yops is to block phagocytes to engulf the pathogen. This is achieved by a specific mechanism denoted polarized translocation. The bacterium first interacts with the target cell; this intimate binding triggers increased Yop-expression followed by Yop-secretion. The Yop-effectors are then translocated into the cytosol of the target cell across the plasma membrane but only as the zone of contact between the bacterium and the eukaryotic cell. Once in the cytosol the Yop-effectors disarm the phagocyte so it can not take up the pathogen. Polarized Yop-translocation can be divided into following steps:i) The pathogen first bind to the surface of the target cell. This intimate contact leads to increased Yop-expression. ii) The bacterium secretes thereafter the Yops via the Type III secretion machinery but only at the zone of contact between the pathogen and the target cell. iii) The Yop-effectors are translocated across the target cell membrane guided by LcrV, YopB and YopD. iv) The Yop-effectors interact with their respective molecular targets to disarm the eukaryotic cell. Our aims are to dissect this chain of events on the molecular level.
We have recently employed chemical genetics in attempts to further dissect the T3SS. A class of small molecules have been identified that specifically blocks T3S of Yersinia as well as Salmonella, Pseudomonas and Chlamydia. These virulence blocking agens have the potential to be developed into a new class of antibacterial agens. We are presently pursuing this idea.
