The Type II and Tad Secretion Systems in Bacterial Pathogenesis

Bacterial secretion systems release effectors into the extra-cellular milieu or directly into foreign cells. They represent fundamental mechanisms by which bacteria modulate their environment and induce human infection. Here we study two related and complementary secretion systems, the bacterial type II secretion system (T2SS) and the Tad secretion system (TdSS). The T2SS secretes effectors and toxins involved in cell adherence, biofilm formation and host cell death. The TdSS drives cell adherence and colonization through extra-cellular pilus formation. Both secretion systems constitute multi-component complexes with many shared components that span the cell envelope of Gram-Negative bacteria. The overall goal is to determine the molecular mechanism underlying T2SS and TdSS operation. Key aims for the T2SS include showing how substrate is recruited, how inner membrane components are organised, and how pseudo-pilus assembly is coordinated. The repertoire of K. pneumoniae T2SS virulence factors will also be expanded. For the TdSS, key aims include structure-function studies on the outer membrane secretin with its associated pilotin and pilus. Comparison of T2SS and TdSS structures will reveal common mechanistic and evolutionary principles. By understanding how the T2SS and TdSS function and promote pathogenesis, this research has the potential to facilitate drug development and combat anti-microbial resistance.