Type IV secretion systems: tools of bacterial horizontal gene transfer and virulence

Abstract

Type IV secretion systems (T4SSs) are multisubunit cell-envelope-spanning structures, ancestrally related to bacterial conjugation machines, which transfer proteins and nucleoprotein complexes across membranes. T4SSs mediate horizontal gene transfer, thus contributing to genome plasticity and the evolution of pathogens through dissemination of antibiotic resistance and virulence genes. Moreover, T4SSs are also used for the delivery of bacterial effector proteins across the bacterial membrane and the plasmatic membrane of eukaryotic host cell, thus contributing directly to pathogenicity. T4SSs are usually encoded by multiple genes organized into a single functional unit. Based on a number of features, the organization of genetic determinants, shared homologies and evolutionary relationships, T4SSs have been divided into several groups. Type F and P (type IVA) T4SSs resembling the archetypal VirB/VirD4 system of Agrobacterium tumefaciens are considered to be the paradigm of type IV secretion, while type I (type IVB) T4SSs are found in intracellular bacterial pathogens, Legionella pneumophila and Coxiella burnetii. Several novel T4SSs have been identified recently and their functions await investigation. The most recently described GI type T4SSs play a key role in the horizontal transfer of a wide variety of genomic islands derived from a broad spectrum of bacterial strains.

Fig. 1

Conjugation. Conjugation systems (shown is the shot-and-pump model of conjugative DNA transfer) represent a large subfamily of the T4SSs and are used by bacteria in the process of the conjugative transfer of DNA from donor to recipient cells (A) by cell-to-cell contact usually mediated by the retraction of the pilus-like structures (B). C. ssDNA of the mobile genetic element is transferred from the donor to recipient bacteria with the help of the relaxase. D. Complementary DNA strands are synthesized in both cells and the former recipient bacterium becomes a new potential donor of the mobile DNA.

Fig. 2

Model of the VirB/VirD4 type IV secretion machinery of Agrobacterium tumefaciens. The T4SS of A. tumefaciens is a multicomponent cell-envelope spanning structure that consists of 11 VirB proteins VirB1–VirB11 and VirD4. Colour code: yellow, nucleoside triphosphatases that provide energy for the transfer; blue, components of the transmembrane channel; red, pilus-forming components; green, lytic transglycosylase responsible for the degradation of the murein (peptidoglycan) layer at the site of assembly.

Fig. 3

The variable T4SSs. The picture shows genetic organization of the GI T4SS in three known sublineages (ICEHin1056, pKLC102/PAPI, SPI-7) and its homologues in paradigmal F and P-like T4SSs and I-like T4SSs. GI T4SSs are well conserved in genomic islands from different bacterial species and share only limited homology to few components of the F- and P- and I-like T4SSs. Genes homologous across T4SS groups are highlighted with the same colour. Upper case gene names = Tra, Icm and lower case gene names = Trb, Dot for F plasmid and L. pneumophila respectively.