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Chapter 10 : Mechanism and Function of Type IV Secretion During Infection of the Human Host

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Abstract:

Bacterial type IV secretion systems (T4SSs) are widely distributed among Gram-negative and Gram-positive bacteria. These systems contribute in various ways to infection processes among clinically important pathogens, including , and species, , and ( ). The list of pathogens employing T4SSs to subvert host cellular pathways for establishment of a replication niche continues to expand, making these machines an important subject of study for defining critical features of disease progression and development of strategies aimed at suppressing T4SS function ( ). Also of importance, studies of T4SSs and effector functions have coincidentally and appreciably augmented our understanding of basic cellular processes in the human host.

Citation: Gonzalez-Rivera C, Bhatty M, Christie P. 2016. Mechanism and Function of Type IV Secretion During Infection of the Human Host, p 265-303. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0024-2015
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Figure 1

Bacterial pathogens employing type IV secretion systems (T4SSs) for establishment within the human host, acquisition of DNA encoding virulence traits, or out-competition of other bacteria for niche occupation. Extracellular pathogens deliver substrates to human or plant cells by contact-dependent or -independent mechanisms. These pathogens deliver diverse substrates including oncogenic T-DNA, monomeric CagA, and multimeric pertussis toxin. Facultative intracellular pathogens enter the host cell from an environmental sample, whereas obligate intracellular pathogens enter directly from another host cell. The intracellular pathogens employ T4SSs to deliver a myriad of effectors whose collective function is to subvert host cellular processes principally for establishment of replicative niches. Shown are T4SSs on the bacterial cell envelope (red trapezoids), effectors (proteins: multicolor circles; tDNA: red wavy line), and various target organelles/sites of effector action within the host cell. T4SSs also mediate interbacterial transfer by contact-dependent mechanisms for conjugative DNA transfer or to kill neighboring bacteria (red X), or by contact-independent mechanisms to exchange DNA with the environment.

Citation: Gonzalez-Rivera C, Bhatty M, Christie P. 2016. Mechanism and Function of Type IV Secretion During Infection of the Human Host, p 265-303. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0024-2015
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Image of Figure 2
Figure 2

Schematic of the VirB/VirB type IV secretion system (T4SS). (Lower) genes are expressed from the same promoter, and from a separate promoter (indicated by two slashes). (Upper) The VirB and VirD4 subunits assemble as the translocation channel, which presents as two subcomplexes termed the outer membrane complex (OMC), composed of VirB7, VirB9, VirB10, and VirB2, and the inner membrane complex (IMC), composed of VirB3, VirB4, VirB6, VirB8, VirB11, and VirD4. VirB2, VirB5, and a proteolytic fragment of VirB1 (B1*) also assemble as the conjugative pilus without a requirement for VirD4. The physical and functional relationships between the translocation channel and the conjugative pilus are not yet known. OM, outer membrane; CW, cell wall; CM, cytoplasmic membrane. See references , and for recent structures of related T4SSs. Adapted from 2013. The expanding bacterial type IV secretion lexicon. Res Microbiol 620–629. Copyright 2013, Institut Pasteur, published by Elsevier Masson SAS. All rights reserved.

Citation: Gonzalez-Rivera C, Bhatty M, Christie P. 2016. Mechanism and Function of Type IV Secretion During Infection of the Human Host, p 265-303. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0024-2015
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Image of Figure 3
Figure 3

Type IV secretion system effectors and cellular consequences of translocation by extracellular pathogens. and deliver substrates through direct cell–cell contact, and does so by a contact-independent mechanism. Pathogens target the host cell types listed. Translocated effectors interact (red arrows; dash denotes indirect interaction) with host cell proteins (light green boxes) to modulate various cellular processes and signaling pathways. Cellular consequences of the effector–host protein interactions (black arrows) are listed (aqua boxes).

Citation: Gonzalez-Rivera C, Bhatty M, Christie P. 2016. Mechanism and Function of Type IV Secretion During Infection of the Human Host, p 265-303. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0024-2015
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Image of Figure 4
Figure 4

Type IV secretion system (T4SS) effectors and cellular consequences of translocation by intracellular pathogens. The pathogens listed deliver effector proteins to establish a replicative niche within phagosomal compartments. Associated with each organism is the name of the T4SS, the replicative niche (e.g., LCV for -containing vacuole), the host cell type(s) targeted, and the current number of known or estimated effectors. Also for each organism is a list of representative effectors and cellular consequences of their activity within the host cell (colored boxes).

Citation: Gonzalez-Rivera C, Bhatty M, Christie P. 2016. Mechanism and Function of Type IV Secretion During Infection of the Human Host, p 265-303. In Kudva I, Cornick N, Plummer P, Zhang Q, Nicholson T, Bannantine J, Bellaire B (ed),

Virulence Mechanisms of Bacterial Pathogens, Fifth Edition

. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.VMBF-0024-2015
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