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

Ashley Clarke1, Isabelle M Llabona1, Nimra Khalid1

  • 1Department of Infectious Diseases & Immunology, University of Florida , Gainesville, Florida, USA.

Microbiology Spectrum
|October 6, 2023
PubMed
Abstract

Insights

Tolfenpyrad, a pesticide, effectively inhibits pathogenic Francisella growth. Researchers identified Francisella novicida mutations conferring resistance and a regulator affecting sensitivity to tolfenpyrad and reactive oxygen species.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Francisella species are highly pathogenic bacteria posing a global health security threat.
  • Existing antibiotics are insufficient, and no protective vaccine is available against Francisella.
  • The potential for Francisella to be developed as bioweapons necessitates novel treatment strategies.

Purpose of the Study:

  • To identify potential new therapeutic agents against Francisella infections.
  • To investigate the efficacy of the pesticide tolfenpyrad as an antimicrobial treatment.
  • To understand the mechanisms of resistance and sensitivity to tolfenpyrad in Francisella.

Main Methods:

  • Screening of existing drugs for activity against Francisella.
  • Antimicrobial susceptibility testing of Francisella with tolfenpyrad.
  • Genetic analysis to identify mutations conferring resistance to tolfenpyrad in Francisella novicida.
  • Characterization of transcriptional regulators involved in Francisella novicida sensitivity.

Main Results:

  • Tolfenpyrad demonstrated significant inhibition of Francisella growth.
  • Specific mutations in Francisella novicida were identified that confer resistance to tolfenpyrad.
  • A transcriptional regulator essential for sensitivity to both tolfenpyrad and reactive oxygen species was characterized.

Conclusions:

  • Tolfenpyrad is a promising candidate for development as a novel antibiotic against Francisella due to its established safety profile.
  • Understanding resistance mechanisms is crucial for the effective clinical application of tolfenpyrad.
  • The identified transcriptional regulator provides insights into Francisella's response to oxidative stress and potential drug treatments.
Keywords:
Francisellaantibioticsreactive oxygen speciessmall molecule inhibitortularemia

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