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Discovery of an archetypal protein transport system in bacterial outer membranes

Nature Structural & Molecular Biology volume 19, pages 506–510 (2012)Cite this article

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Abstract

Bacteria have mechanisms to export proteins for diverse purposes, including colonization of hosts and pathogenesis. A small number of archetypal bacterial secretion machines have been found in several groups of bacteria and mediate a fundamentally distinct secretion process. Perhaps erroneously, proteins called 'autotransporters' have long been thought to be one of these protein secretion systems. Mounting evidence suggests that autotransporters might be substrates to be secreted, not an autonomous transporter system. We have discovered a new translocation and assembly module (TAM) that promotes efficient secretion of autotransporters in proteobacteria. Functional analysis of the TAM in Citrobacter rodentium, Salmonella enterica and Escherichia coli showed that it consists of an Omp85-family protein, TamA, in the outer membrane and TamB in the inner membrane of diverse bacterial species. The discovery of the TAM provides a new target for the development of therapies to inhibit colonization by bacterial pathogens.

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Figure 1: TamA and the Omp85 superfamily of proteins.
Figure 2: TamA and TamB are membrane proteins interacting to form the TAM.
Figure 3: p1121 is an autotransporter and substrate of the TAM.
Figure 4: Bacteria lacking the TAM are ineffective in the assembly of autotransporters.
Figure 5: Overview of the Omp85 family machinery in Gram-negative bacteria.

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Acknowledgements

We thank D. Daley from the Department of Chemistry and Biophysics at Stockholm University for reagents, J. Rossjohn for critical discussions and A. Traven and T. Beilharz for critical comments on the manuscript. This work was made possible by the National Health & Medical Research Council (NHMRC) of Australia through an NHMRC Project grant (508911, to T.L. and A.W.P.), an NHMRC Program grant (606788, to T.L., E.L.H. and R.A.S.), an ARC Super Science grant (to T.L. and R.A.S.) and a BBSRC New Investigator grant to D.W. T.L. is an Australian Research Council Federation Fellow, E.L.H. and M.A.S. are ARC Future Fellows, A.W.P. is an NHMRC Senior Research Fellow, C.T.W., M.J.B. and A.J.P. are NHMRC Biomedical Fellows, D.L.L. is an ARC Super Science Fellow and J.S. is supported by an NHMRC Postgraduate Research Scholarship.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia

    Joel Selkrig, Chaille T Webb, Matthew J Belousoff, Andrew J Perry, Denisse L Leyton, Nermin Celik & Trevor Lithgow

  2. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK

    Khedidja Mosbahi & Daniel Walker

  3. The School of Immunity and Infection, University of Birmingham, Edgbaston, UK

    Timothy J Wells, Faye Morris, Denisse L Leyton & Ian R Henderson

  4. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia

    Makrina Totsika, Minh-Duy Phan & Mark A Schembri

  5. Department of Microbiology and Immunology, The University of Melbourne, Parkville, Australia

    Michelle Kelly, Clare Oates, Elizabeth L Hartland, Roy M Robins-Browne & Richard A Strugnell

  6. Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia

    Roy M Robins-Browne

  7. Department of Biochemistry & Molecular Biology, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Australia

    Sri Harsha Ramarathinam & Anthony W Purcell

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Contributions

J.S. initiated the project. J.S., C.T.W., M.-D.P., A.J.P., N.C., K.M. and M.J.B. conducted experiments and data analysis. I.R.H., T.J.W., F.M., M.T., R.M.R.-B., M.D.-P., C.O., E.L.H. D.W. and M.K. engineered bacterial strains and conducted experiments and data analysis. A.W.P. and S.H.R carried out and analyzed data from MS experiments. T.L. supervised the project, and T.L., J.S., C.T.W., M.J.B., R.A.S., I.R.H., D.L.L. and M.A.S. contributed to writing the manuscript.

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Correspondence to Trevor Lithgow.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 418 kb)

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Selkrig, J., Mosbahi, K., Webb, C. et al. Discovery of an archetypal protein transport system in bacterial outer membranes. Nat Struct Mol Biol 19, 506–510 (2012). https://doi.org/10.1038/nsmb.2261

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