Type IV Secretion in Agrobacterium tumefaciens and Development of Specific Inhibitors

The Agrobacterium tumefaciens VirB/D4 type IV secretion system (T4SS) comprises 12 membrane-bound proteins, and it assembles a surface-exposed T-pilus. It is considered to be the archetypical system that is generally used to orient the nomenclature of other T4SS. Whereas the sequence similarities between T4SSs from different organisms are often limited, the general mechanism of action appears to be conserved, and the evolutionary relationship to bacterial conjugation systems and to T4SSs from animal pathogens is well established. Agrobacterium is a natural genetic engineer that is extensively used for the generation of transgenic plants for research and for agro-biotechnological applications. It also served as an early model for the understanding of pathogen-host interactions and for the transfer of macromolecular virulence factors into host cells. The knowledge on the mechanism of its T4SS inspired the search for small molecules that inhibit the virulence of bacterial pathogens and of bacterial conjugation. Inhibitors of bacterial virulence and of conjugation have interesting potential as alternatives to antibiotics and as inhibitors of antimicrobial resistance gene transfer. Mechanistic work on the Agrobacterium T4SS will continue to inspire the search for inhibitor target sites and drug design.