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Review
. 2003 Nov;1(2):137-49.
doi: 10.1038/nrmicro753.

The versatile bacterial type IV secretion systems

Eric Cascales  1 , Peter J Christie
Affiliations
Review

The versatile bacterial type IV secretion systems

Eric Cascales et al. Nat Rev Microbiol. 2003 Nov.

Abstract

Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesis--genetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection.

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Figures

Figure 1
Figure 1. Schematic representation of the different type-IV-dependent mechanisms
The three subfamilies of type IV secretion (T4S) systems are shown. Conjugation machines deliver DNA to recipient bacteria and other cell types by cell-to-cell contact. DNA-uptake and -release systems exchange DNA with the extracellular milieu independently of contact with target cells. Effector translocators deliver DNA or protein substrates to eukaryotic cells during infection. The effector translocators contribute in markedly different ways to the infection processes of the bacterial pathogens shown. PT, pertussis toxin.
Figure 2
Figure 2. Topologies of the VirB/D4 subunits of the A. tumefaciens type IV secretion (T4S) system
The coupling protein (CP) VirD4 and the mating-pore-formation components (VirB1–VirB11) are represented according to their proposed functions: energetic (blue), channel (red) or pilus (green) components. Several proteins are post-translationally modified in the periplasm. Signal sequences of VirB1, VirB2, VirB5, VirB7 and VirB9 are cleaved by signal peptidases. VirB1 is processed to form VirB1*, which is exported across the outer membrane. VirB2 undergoes a novel head-to-tail cyclization reaction, and polymerizes as the T-pilus. VirB7 is modified as a lipoprotein that associates with the T-pilus and also forms an intermolecular disulphide crosslink with VirB9, a possible secretin. The VirB and VirD4 proteins are postulated to assemble as a supramolecular structure composed of a transenvelope channel and an extracellular pilus.
Figure 3
Figure 3. Models of type IV secretion (T4S) system-mediated substrate translocation
The Agrobacterium tumefaciens VirB/D4 system is presented as a model (a), with the possible architecture in accordance with the results of topological (Fig. 2) and interaction (Table 2) studies. Two working models are depicted – the ‘channel’ model in which the pilus acts as a channel for passage of the substrate across the cell envelope, and the ‘piston’ model in which the pilus acts as a piston motor, pushing the substrates to the medium or into the eukaryotic cell. Possible translocation routes are represented (blue arrows represent protein substrates; red arrows represent DNA substrates). DNA and protein substrates might be translocated through the same or different pathways, using the coupling protein (CP; for example, VirD4), the mating-pore-formation (Mpf) complex, the general secretion pathway (GSP) or another pathway for secretion across the inner membrane. The Mpf structure is used to deliver substrates across the outer membrane. The competence model (b) is shown as a comparison.
Figure 4
Figure 4. Schematic representation of the cellular consequences of type IV secretion (T4S) system effector translocation
T4S effector translocation alters various eukaryotic cellular processes, as illustrated for the four systems in which effector molecules have been identified so far. Agrobacterium tumefaciens delivery of T-DNA and effector proteins induces synthesis of opine food substrates and also induces tumour production through modulation of phytohormone levels. Helicobacter pylori CagA modulates various pathways associated with eukaryotic-cell differentiation, proliferation and motility. Bordetella pertussis pertussis toxin (PT) interferes with G-protein-dependent signalling pathways, and Legionella pneumophila RalF recruits the ARF (ADP ribosylation factor) family of guanosine triphosphatases to the phagosome to promote intracellular survival.
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