Discovery and Biological Characterization of the Auromomycin Chromophore as an Inhibitor of Biofilm Formation in Vibrio cholerae

Authors

  • Kelly C. Peach,

    1. Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (USA)
    Search for more papers by this author
  • Andrew T. Cheng,

    1. Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (USA)
    Search for more papers by this author
  • Allen G. Oliver,

    1. Molecular Structure Facility, Department of Chemistry and Biochemistry, University of Notre Dame, 246 Nieuwland Science Hall, Notre Dame, IN 46556 (USA)
    Search for more papers by this author
  • Prof. Fitnat H. Yildiz,

    1. Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (USA)
    Search for more papers by this author
  • Prof. Roger G. Linington

    Corresponding author
    1. Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (USA)
    • Department of Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz, CA 95064 (USA)

    Search for more papers by this author

Abstract

Bacterial biofilms pose a significant challenge in clinical environments due to their inherent lack of susceptibility to antibiotic treatment. It is widely recognized that most pathogenic bacterial strains in the clinical setting persist in the biofilm state, and are the root cause of many recrudescent infections. The discovery and development of compounds capable of either inhibiting biofilm formation or initiating biofilm dispersal might provide new therapeutic avenues for reducing the number of hospital-acquired, biofilm-mediated infections. We detail here the application of our recently reported image-based, high-throughput screen to the discovery of microbially derived natural products with inhibitory activity against Vibrio cholerae biofilm. Examination of a prefractionated library of microbially derived marine natural products has led to the identification of a new biofilm inhibitor that is structurally unrelated to previously reported inhibitors and is one of the most potent inhibitors of V. cholerae reported to date. Combination of this compound with sub-MIC concentrations of a number of clinically relevant antibiotics was shown to improve the inhibitory efficacy of this new compound compared to monotherapy treatments, and provides evidence for the potential therapeutic benefit of biofilm inhibitors in treating persistent biofilm-mediated infections.

Ancillary