Quorum-sensing control of antibiotic resistance stabilizes cooperation in Chromobacterium violaceum

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Many Proteobacteria use quorum sensing to regulate production of public goods, such as antimicrobials and proteases, that are shared among members of a community. Public goods are vulnerable to exploitation by cheaters, such as quorum sensing-defective mutants. Quorum sensing- regulated private goods, goods that benefit only producing cells, can prevent the emergence of cheaters under certain growth conditions. Previously, we developed a laboratory co-culture model to investigate the importance of quorum-regulated antimicrobials during interspecies competition. In our model, Burkholderia thailandensis and Chromobacterium violaceum each use quorum sensing-controlled antimicrobials to inhibit the other species’ growth. Here, we show that C. violaceum uses quorum sensing to increase resistance to bactobolin, a B. thailandensis antibiotic, by increasing transcription of a putative antibiotic efflux pump. We demonstrate conditions where C. violaceum quorum-defective cheaters emerge and show that in these conditions, bactobolin restrains cheaters. We also demonstrate that bactobolin restrains quorum-defective mutants in our co-culture model, and the increase in antimicrobial-producing cooperators drives the C. violaceum population to become more competitive. Our results describe a mechanism of cheater restraint involving quorum control of efflux pumps and demonstrate that interspecies competition can reinforce cooperative behaviors by placing constraints on quorum sensing-defective mutants.

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We thank Nikolas Skye Robins, Amy Schaefer, Ben Kerr, Chris Waters, Ajai Dandekar. and John Henry Kimbrough for helpful discussions and Stuart Macdonald for technical expertize. This work was supported by startup funds from the University of Kansas to JRC and a NIH COBRE Center for Molecular Analysis of Disease Pathways Research Project Award to JRC (P20GM103638). KCE was supported by the NIH Chemical Biology Training program (T32 GM08545). LC was supported by the NIH Post-Baccalaureate Research Education program (R25GM078441). EBN was supported by a KU Undergraduate Research Award. BN was supported by the NIH KU Legacy Chemical Methodologies and Library Development program (R24GM111385) and the COBRE CMADP Chemical Biology Core (P20GM103638 and P20GM113117). XW was supported by the NIH K-INBRE program (P20GM103418). We thank the COBRE CMADP Genome Sequencing Core (P20GM103638) for library preparation and the K-INBRE Bioinformatics Core (P20GM103418) for providing help with mutant analysis. The content in this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author information


  1. Department of Molecular Biosciences, University of Kansas, Lawrence, KS, 66045, USA

    • Kara C Evans
    • , Saida Benomar
    • , Lennel A Camuy-Vélez
    • , Ellen B Nasseri
    • , Xiaofei Wang
    •  & Josephine R Chandler
  2. Chemical Methodologies and Library Development Legacy, University of Kansas, Lawrence, KS, 66045, USA

    • Benjamin Neuenswander
  3. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724, USA

    • Xiaofei Wang


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Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Josephine R Chandler.

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