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Type VI secretion system effectors: poisons with a purpose

Nature Reviews Microbiology volume 12, pages 137–148 (2014)Cite this article

Subjects

Key Points

  • Many bacteria exist in complex communities that consist of dense populations that are in close contact and in competition for shared resources.

  • The Gram-negative type VI secretion system (T6SS) has recently emerged as a potent contact-dependent pathway for mediating bacterial interactions.

  • Effector proteins that are translocated by the T6SS disrupt multiple essential and conserved features of bacterial physiology.

  • Regulatory, biochemical, and genomic data are consistent with a role for the T6SS and its associated effectors in directly contributing to fitness when bacteria are in competition with one another.

  • The T6SS seems to have the capacity to participate in direct cell-to-cell signalling, and potentially has an important role in the coordination of social behaviours and the maintenance of cooperative groups.

  • The presence of the T6SS both in pathogens that are common in polymicrobial sites of infection and in organisms of environmental interest suggests that the effects that are mediated by the pathway might have an important role in the dynamics of these habitats and so affect both human health and the success of attempts to manipulate native bacterial communities.

Abstract

The type VI secretion system (T6SS) mediates interactions between a broad range of Gram-negative bacterial species. Recent studies have led to a substantial increase in the number of characterized T6SS effector proteins and a more complete and nuanced view of the adaptive importance of the system. Although the T6SS is most often implicated in antagonism, in this Review, we consider the case for its involvement in both antagonistic and non-antagonistic behaviours. Clarifying the roles that type VI secretion has in microbial communities will contribute to broader efforts to understand the importance of microbial interactions in maintaining human and environmental health, and will inform efforts to manipulate these interactions for therapeutic or environmental benefit.

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Figure 1: T6SS effectors target varying aspects of bacterial physiology.
Figure 2: Multiple roles for interbacterial T6S.
Figure 3: Interbacterial T6S and infection.

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Acknowledgements

The authors thank members of the Mougous laboratory for insightful discussions. This work was supported by grants from the US National Institutes of Health (AI080609 and AI057141) and Cystic Fibrosis Foundation (CFR565-CR07). A.B.R. was supported by a Graduate Research Fellowship from the National Science Foundation (DGE-0718124), and J.D.M. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund.

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  1. Department of Microbiology, University of Washington, Seattle, 98195, Washington, USA

    Alistair B. Russell, S. Brook Peterson & Joseph D. Mougous

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  1. Alistair B. Russell
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Correspondence to Joseph D. Mougous.

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Glossary

Haemolysin co-regulated protein

(Hcp). A ring-shaped substrate and structural component of the type VI secretion system. It is structurally related to the T4 bacteriophage tail tube protein gp19.

Sacculus

The total cell wall structure (which contains peptidoglycan and associated molecules) of a bacterium; the term derives from the appearance of isolated cell wall superstructures as meshwork bags.

Type IV secretion systems

Secretion systems involved in the transfer of both DNA and proteins to bacterial and eukaryotic targets.

Valine–glycine repeat protein G

(VgrG). A substrate and structural component of the type VI secretion system (T6SS). It is structurally related to the T4 bacteriophage tail spike apparatus, gp27 and gp5.

Bacteriocins

Proteins released by bacteria that exerts toxic effects on related organisms. Bacteriocins and specific immunity determinants that protect the producing cell are typically encoded by adjacent genes.

Recombination hotspot proteins

(Rhs proteins). Large multi-domain proteins that have a central element consisting of a repeating motif and a toxin domain at their carboxyl terminus. They were initially identified as sites of frequent recombination in the Escherichia coli genome.

Quorum sensing

An interbacterial signalling system in which signal concentration correlates with cell density, thus providing a measure of the local concentration of signal-producing organisms.

Toxin–antitoxin systems

(TA systems). Systems that consist of a toxic element and an unstable cognate antitoxin that mediate toxicity in the producing cell such that depletion of the antitoxin results in death or senescence of the organism.

Viable but non-culturable

(VBNC). Describes a growth state in which a cell is not actively dividing but in which viability is maintained.

Cooperation

The investment of resources by one individual into a process that benefits other individuals. Cooperation is not necessarily mutually beneficial.

Phyllosphere

A habitat that consists of the above-ground surfaces of plants, particularly the leaves.

Rhizosphere

A habitat that consists of plant roots and the surrounding soil that is influenced by their secretions.

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Russell, A., Peterson, S. & Mougous, J. Type VI secretion system effectors: poisons with a purpose. Nat Rev Microbiol 12, 137–148 (2014). https://doi.org/10.1038/nrmicro3185

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