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Conditional toxicity and synergy drive diversity among antibacterial effectors

Nature Microbiologyvolume 3pages440446 (2018) | Download Citation


Bacteria in polymicrobial habitats contend with a persistent barrage of competitors, often under rapidly changing environmental conditions1. The direct antagonism of competitor cells is thus an important bacterial survival strategy2. Towards this end, many bacterial species employ an arsenal of antimicrobial effectors with multiple activities; however, the benefits conferred by the simultaneous deployment of diverse toxins are unknown. Here we show that the multiple effectors delivered to competitor bacteria by the type VI secretion system (T6SS) of Pseudomonas aeruginosa display conditional efficacy and act synergistically. One of these effectors, Tse4, is most active in high-salinity environments and synergizes with effectors that degrade the cell wall or inactivate intracellular electron carriers. We find Tse4 synergizes with these disparate mechanisms by forming pores that disrupt the ΔΨ component of the proton motive force. Our results provide evidence that the concomitant delivery of a cocktail of effectors serves as a bet-hedging strategy to promote bacterial competitiveness in the face of unpredictable and variable environmental conditions.

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We thank D. Raible for providing pHluorin2 DNA, D. Walker for pyocin S5, the UW Cystic Fibrosis Research Development Program for sequencing, A. Roehrich for ICP-OES training, Tamir Gonen, B. Krantz, K. Ghosal and D. Das for assistance with Tse4 biochemical analysis, T. Kinkel and D. Prunkard for flow cytometry protocol development and analysis, R. Siehnel for assistance with barcode sequences, S. Dove for critical reading of the manuscript, and members of the Mougous laboratory for helpful discussions. This work was funded by the NIH (R01-AI080609 to JDM) and the Defense Threat Reduction Agency (HDTRA1-13-1-0014 to J.D.M.). K.D.L. was supported by the UW Cellular and Molecular Biology Training Grant (T32GM007270), and J.D.M. holds an Investigator in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund and is an HHMI Investigator.

Author information


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

    • Kaitlyn D. LaCourse
    • , S. Brook Peterson
    • , Hemantha D. Kulasekara
    • , Matthew C. Radey
    • , Jungyun Kim
    •  & Joseph D. Mougous
  2. Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA

    • Joseph D. Mougous


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K.D.L., S.B.P., H.D.K. and J.D.M. designed the study. K.D.L., S.B.P., H.D.K, M.C.R., R.K. and J.D.M. performed experiments, and K.D.L., S.B.P., H.D.K., M.C.R. and J.D.M analysed data. K.D.L., S.B.P., and J.D.M. wrote the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Joseph D. Mougous.

Supplementary information

  1. Supplementary Information

    Supplementary Figures 1–5 and Supplementary Tables 1–4.

  2. Life Sciences Reporting Summary

  3. Supplementary Table 1

    Effector repertoires of T6SS-containing Proteobacteria.

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