Structure and Function of the phospholipase/sphingomyelinase PlcHR from P. aeruginosa. (360G-Wellcome-094759_Z_10_Z)

Pseudomonas aeruginosa is an opportunistic pathogen that causes acute infections (sepsis) predominantly in victims with large or burn wounds, chronic infections in immuno-compomised patients such as people in cancer chemotherapy and chronic pulmonary infections and inflammation in cystic fibrosis patients. While a large number of virulent factors expressed and secreted by the pathogen are known, the precise cellular and molecular mechanisms of these remain largely elusive. PlcHR from P. aerugino sa, a complex extracellular toxin represents a major virulence factor that has been shown to be selectively cytotoxic to mammalian endothelial cells that line the interior surface of all blood vessels. They play key roles in thrombosis, inflammation and the formation of new blood vessels. It has therefore been suggested that PlcHR is directly involved in the cellular mechanisms responsible for the vascular lesions and poor wound healing associated with P. aeruginosa septicemia and sepsis. Furth ermore, PlcHR has been shown to exhibit strong anti-angiogenic attributes that could be exploited for example in the treatment of tumors. Deciphering the molecular basis of PlcHR activity is therefore of major medical importance.