Proteases and bacterial virulence: a view from the trenches

Many species of pathogenic bacteria produce cell-surface or secreted proteases. These enzymes have high potential to enhance bacterial pathogenesis through degradation of critical host proteins and by mimicking the activity of host regulatory proteases that control important zymogen systems. Although many bacterial proteases have been implicated in virulence, there is currently no system in which both rigorous demonstration of virulence enhancement in vivo and convincing identification of the important substrate molecules has been achieved. The difficulties inherent in addressing these issues is discussed, and several interesting systems under active investigation briefly described. The potential of extracellular protease as targets for drug development is also considered.