16 Bacterial Type IV Secretion Systems: DNA Conjugation Machines Adapted for Export of Virulence Factors

Pathogenic bacteria of humans and plants have coopted conjugation systems to export virulence factors to eukaryotic host cells. Although this is a functionally diverse family, there are some unifying themes: (i) exporters are assembled at least in part from subunits of DNA conjugation systems, and (ii) the known substrates recognized by these transporters are large macromolecules such as nucleoprotein particles, scaffolding proteins, guanine nucleotide exchange factors, or multisubunit toxins. The type IV secretion family is composed of toxin exporters used by several bacterial human pathogens. Bordetella pertussis, the causative agent of whooping cough, uses the Ptl transporter to export the AB type pertussis toxin across the bacterial envelope. The growing list of pathogens that utilize type IV secretion system (TFSS) for delivery of effector molecules into the host cell environment, comprising species like Brucella, Actinobacillus, Ehrlichia, Wolbachia, and Xilella, is under continuous revision. The existence of a subset of VirB homologues in the Helicobacter pylori cag and Legionella pneumophila icm/dot systems underscores the functional importance of these types of proteins in macromolecular export. The Agrobacterium tumefaciens T-DNA-processing reaction resembles the conjugative DNA-processing reaction, resulting in formation of the T-strand/ VirD2/VirE2 nucleoprotein particle or T complex. Perhaps the most compelling evidence that conjugation machines recognize proteins as translocationcompetent substrates is that VirE2 SSB can be exported to plant cells independently of the T-strand/VirD2 complex. The evolution of a family of secretion systems from ancestral DNA conjugation machines raises many interesting questions and exciting new research directions.