The outs and ins of bacterial type IV secretion substrates.

Bacteria use type IV secretion systems (T4SS) to translocate macromolecular substrates destined for bacterial, plant or human target cells. The T4SS are medically important, contributing to virulence-gene spread, genome plasticity and the alteration of host cellular processes during infection. The T4SS are ancestrally related to bacterial conjugation machines, but present-day functions include (i) conjugal transfer of DNA by cell-to-cell contact, (ii) translocation of effector molecules to eukaryotic target cells, and (iii) DNA uptake from or release to the extracellular milieu. Rapid progress has been made toward identification of type IV secretion substrates and the requirements for substrate recognition.