Tolfenpyrad displays Francisella-targeted antibiotic activity that requires an oxidative stress response regulator for sensitivity

  • Microbiol Spectr. 2023 Dec 12;11(6):e0271323. doi: 10.1128/spectrum.02713-23.
Ashley Clarke  #  1 ,  Isabelle M Llabona  #  1 ,  Nimra Khalid  1 ,  Danielle Hulvey  1 ,  Alexis Irvin  1 ,  Nicole Adams  1 ,  Henry S Heine  2 ,  Aria Eshraghi  1  3  4
Affiliations
  • 1. Department of Infectious Diseases & Immunology, University of Florida , Gainesville, Florida, USA.
  • 2. Institute for Therapeutic Innovation, University of Florida , Orlando, Florida, USA.
  • 3. Emerging Pathogens Institute, University of Florida , Gainesville, Florida, USA.
  • 4. Department of Oral Biology, University of Florida , Gainesville, Florida, USA.
  • # Contributed equally.
PMID: 37800934 DOI: 10.1128/spectrum.02713-23
Abstract

Francisella species are highly pathogenic bacteria that pose a threat to global health security. These bacteria can be made resistant to Antibiotics through facile methods, and we lack a safe and protective vaccine. Given their history of development as bioweapons, new treatment options must be developed to bolster public health preparedness. Here, we report that tolfenpyrad, a pesticide that is currently in use worldwide, effectively inhibits the growth of Francisella. This drug has an extensive history of use and a plethora of safety and toxicity data, making it a good candidate for development as an Antibiotic. We identified mutations in Francisella novicida that confer resistance to tolfenpyrad and characterized a transcriptional regulator that is required for sensitivity to both tolfenpyrad and Reactive Oxygen Species.

Keywords
Francisella; antibiotics; reactive oxygen species; small molecule inhibitor; tularemia.
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