The toxin/immunity network of Burkholderia pseudomallei contact-dependent growth inhibition (CDI) systems

Authors

  • Kiel Nikolakakis,

    1. Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA
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    • These primary authors contributed equally to the work.

  • Saba Amber,

    1. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA
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    • These primary authors contributed equally to the work.

  • J. Scott Wilbur,

    1. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA
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    • Present addresses: Vet. Sciences Micro Dept., 1117 E. Lowell St., Bld. 90, Room 301, University of Arizona, Tucson, AZ 85721;

  • Elie J. Diner,

    1. Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA, USA
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    • 415 Life Sciences Addition (LSA), University of California, Berkeley, CA 94720;

  • Stephanie K. Aoki,

    1. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA
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    • ETH Zürich, D-BSSE, WRO-1058, Warenannahme WRO-1007.P.18,Mattenstrasse 22,CH-4058 Basel, Switzerland;

  • Stephen J. Poole,

    1. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA
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  • Apichai Tuanyok,

    1. Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA
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  • Paul S. Keim,

    1. Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA
    2. The Translational Genomics Research Institute, Flagstaff, AZ, USA
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  • Sharon Peacock,

    1. Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Bangkok, Thailand
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    • Departments of Medicine and Pathology, University of Cambridge, Cambridge, UK.

  • Christopher S. Hayes,

    1. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA
    2. Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA, USA
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    • These senior authors contributed equally to this work.

  • David A. Low

    Corresponding author
    1. Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA
    2. Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA, USA
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    • These senior authors contributed equally to this work.


Summary

Burkholderia pseudomallei is a category B pathogen and the causative agent of melioidosis – a serious infectious disease that is typically acquired directly from environmental reservoirs. Nearly all B. pseudomallei strains sequenced to date (> 85 isolates) contain gene clusters that are related to the contact-dependent growth inhibition (CDI) systems of γ-proteobacteria. CDI systems from Escherichia coli and Dickeya dadantii play significant roles in bacterial competition, suggesting these systems may also contribute to the competitive fitness of B. pseudomallei. Here, we identify 10 distinct CDI systems in B. pseudomallei based on polymorphisms within the cdiA-CT/cdiI coding regions, which are predicted to encode CdiA-CT/CdiI toxin/immunity protein pairs. Biochemical analysis of three B. pseudomallei CdiA-CTs revealed that each protein possesses a distinct tRNase activity capable of inhibiting cell growth. These toxin activities are blocked by cognate CdiI immunity proteins, which specifically bind the CdiA-CT and protect cells from growth inhibition. Using Burkholderia thailandensis E264 as a model, we show that a CDI system from B. pseudomallei 1026b mediates CDI and is capable of delivering CdiA-CT toxins derived from other B. pseudomallei strains. These results demonstrate that Burkholderia species contain functional CDI systems, which may confer a competitive advantage to these bacteria.

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