2. Academic Validation
  3. Tolfenpyrad displays Francisella-targeted antibiotic activity that requires an oxidative stress response regulator for sensitivity

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

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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