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Type VI secretion delivers bacteriolytic effectors to target cells

Nature volume 475, pages 343–347 (2011)Cite this article

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Abstract

Peptidoglycan is the major structural constituent of the bacterial cell wall, forming a meshwork outside the cytoplasmic membrane that maintains cell shape and prevents lysis. In Gram-negative bacteria, peptidoglycan is located in the periplasm, where it is protected from exogenous lytic enzymes by the outer membrane. Here we show that the type VI secretion system of Pseudomonas aeruginosa breaches this barrier to deliver two effector proteins, Tse1 and Tse3, to the periplasm of recipient cells. In this compartment, the effectors hydrolyse peptidoglycan, thereby providing a fitness advantage for P. aeruginosa cells in competition with other bacteria. To protect itself from lysis by Tse1 and Tse3, P. aeruginosa uses specific periplasmically localized immunity proteins. The requirement for these immunity proteins depends on intercellular self-intoxication through an active type VI secretion system, indicating a mechanism for export whereby effectors do not access donor cell periplasm in transit.

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Figure 1: Tse1 and Tse3 are lytic proteins belonging to amidase and muramidase enzyme families.
Figure 2: Tse1 and Tse3 are not required for Tse2 export or transfer to recipient cells via the T6S apparatus.
Figure 3: Tsi1 and Tsi3 provide immunity to cognate toxins.
Figure 4: Tse1 and Tse3 delivered to the periplasm provide a fitness advantage to donor cells.
Figure 5: Proposed mechanism of T6S-dependent delivery of effector proteins.

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Acknowledgements

We thank P. Singh, E. Nester, H. Kulasekara, N. Salama, E. P. Greenberg, L. Ramakrishnan and members of the Mougous laboratory for discussions and critical reading of the manuscript, the Harwood laboratory for use of their microscope, and J. Gray of the Pinnacle Laboratory of Newcastle University for MS analysis. This work was supported by the National Institutes of Health (J.D.M.; RO1 AI080609) and the European Commission within the DIVINOCELL programme (W.V.). A.B.R was supported by a Graduate Research Fellowship from the National Science Foundation.

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Authors and Affiliations

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

    Alistair B. Russell, Rachel D. Hood & Joseph D. Mougous

  2. Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK ,

    Nhat Khai Bui & Waldemar Vollmer

  3. Molecular and Cellular Biology Program, University of Washington, Seattle, 98195, Washington, USA

    Michele LeRoux

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Contributions

A.B.R., R.D.H., N.K.B, M.L., W.V. and J.DM. conceived and designed experiments. A.B.R., R.D.H., N.K.B. and J.D.M conducted experiments. A.B.R., R.D.H., W.V. and J.D.M. wrote the paper.

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Correspondence to Joseph D. Mougous.

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Russell, A., Hood, R., Bui, N. et al. Type VI secretion delivers bacteriolytic effectors to target cells. Nature 475, 343–347 (2011). https://doi.org/10.1038/nature10244

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