T4SSs

Type IV secretion systems (T4SSs) are a family of bacterial machines that transport DNA and/or proteins across the cell envelope. They are best characterized in Gram-negative bacteria and function in two major contexts: horizontal gene transfer by conjugation and delivery of effector proteins into eukaryotic host cells during infection or symbiosis. T4SSs can move DNA alone, protein cargos, or DNA–protein complexes, enabling transfer of genetic material and modulation of host processes.

A T4SS typically comprises a conserved core set of components that assemble into a trans-envelope channel spanning the inner and outer membranes, often accompanied by a surface appendage called a pilus in many systems. The machinery includes coupling proteins that recognize substrates, and ATPases that power assembly and translocation. The components are categorized into Type IVA (for example VirB/VirD4 systems) and Type IVB (for example Dot/Icm systems), which differ in substrate range and architectural details.

Mechanism and substrates involve substrate binding to coupling proteins, followed by energy-dependent translocation through the channel. Some systems extend a pilus to contact recipient cells and deliver substrates, while others secrete directly through a bare channel without a long pilus. In conjugation, DNA transfer spreads plasmids and associated traits; in pathogenesis, effector proteins are delivered to host cells to manipulate signaling and immune responses.

Biological roles and examples include the VirB/VirD4 system of Agrobacterium tumefaciens transferring T-DNA into plant cells, and the Dot/Icm secretion systems of Legionella pneumophila and Coxiella burnetii delivering effectors to host cells. T4SSs are central to horizontal gene transfer and to the manipulation of host-pathogen interactions, making them important subjects of biomedical research.