Towards a systems biology approach to study type II/IV secretion systems.

Many gram-negative bacteria produce thin protein filaments, named pili, which extend beyond the confines of the outer membrane. The importance of these pili is illustrated by the fact that highly complex, multi-protein pilus-assembly machines have evolved, not once, but several times. Their many functions include motility, adhesion, secretion, and DNA transfer, all of which can contribute to the virulence of bacterial pathogens or to the spread of virulence factors by horizontal gene transfer. The medical importance has stimulated extensive biochemical and genetic studies but the assembly and function of pili remains an enigma. It is clear that progress in this field requires a more holistic approach where the entire molecular apparatus that forms the pilus is studied as a system. In recent years systems biology approaches have started to complement classical studies of pili and their assembly. Moreover, continued progress in structural biology is building a picture of the components that make up the assembly machine. However, the complexity and multiple-membrane spanning nature of these secretion systems pose formidable technical challenges, and it will require a concerted effort before we can create comprehensive and predictive models of these remarkable molecular machines.