Mycobactin analogue interacting with siderophore efflux-pump protein: insights from molecular dynamics simulations and whole-cell assays.

Journal: Frontiers in antibiotics
Published Date: May 8, 2024

Abstract

INTRODUCTION: In response to continued public health emergency of antimicrobial resistance (AMR), a significant key strategy is the discovery of novel mycobacterial efflux-pump inhibitors (EPIs) as potential adjuvants in combination drug therapy. Interest in identifying new chemotypes which could potentially synergize with the existing antibiotics and can be deployed as part of a combination therapy. This strategy could delay the emergence of resistance to existing antibiotics and increase their efficacy against resistant strains of mycobacterial species. In recent decades, notable approaches have been accounted for EPI development and have resulted in the discovery of several EPIs including SQ109 and AU1235. In context, to accelerate newer EPIs with novel mode of action here we have discussed mycobactin analogues and highlighted binding orientation with siderophore efflux-pump proteins MmpL4/5.

Authors

  • Mousumi Shyam
    Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Ranchi, India.
  • Abhishek Thakur
    Department of Chemistry, University of Miami, Coral Gables, FL, United States.
  • Caroline Velez
    Department of Chemistry, University of Miami, Coral Gables, FL, United States.
  • Chris Daniel
    Mycobacteria Research Laboratory, Department of Natural Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, London, United Kingdom.
  • Orlando Acevedo
    Department of Chemistry, University of Miami, Coral Gables, FL, United States.
  • Sanjib Bhakta
    Mycobacteria Research Laboratory, Department of Natural Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, London, United Kingdom.
  • Venkatesan Jayaprakash
    Department of Pharmaceutical Sciences & Technology, Birla Institute of Technology, Ranchi, India.

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