Contribution of Francisella tularensis FTL_1306 (dipA) in resazomycin susceptibility


  • Kendall Souder West Liberty University
  • Michael Whaby West Liberty University
  • Jennifer Hickman West Liberty University
  • Donald Primerano Marshall University
  • James Denvir Marshall University
  • Deanna Schmitt West Liberty University


Francisella tularensis, Resazomycins, Resazurin, DipA, Tularemia, Antimicrobial, Antibiotic, Resistance


The CDC classifies Francisella tularensis as a Category A bioterrorism agent. Due to the growing global threat of antibiotic resistant bacteria, novel therapeutics against F. tularensis must be developed.  Resazomycins are resazurin (Rz)-based compounds that exhibit antimicrobial activity against F. tularensis and other gram-negative bacteria. The action of resazomycins is not well understood, but potential targets of the antibiotic were identified in a high throughput screen for Rz-resistant isolates. The dipA (FTL_1306) gene was identified as mutated in half of the 48 Rz-resistant (RZR) strains sequenced. To further investigate the role of dipA in Rz susceptibility, we introduced a wild-type copy of dipA into select RZR isolates (RZR1, 5, 43, and 46) that contain dipA mutations. The dipA gene was amplified by PCR from wild-type F. tularensis and cloned into the F. tularensis shuttle vector pABST to generate a construct (pABST-dipA) in which dipA will be constitutively expressed under control of the groEL promoter. The pABST-dipA plasmid was mobilized into each of the selected RZR isolates by electroporation. Western blotting indicated that expression of wild-type dipA was restored in RZR strains with the introduction of the pABST-dipA construct. The MIC of resazurin for the resulting RZR dipA-complemented strains was equivalent to that wild-type F. tularensis and significantly different from resistant mutants. Further investigation is needed to fully elucidate the contribution of dipA to the bactericidal action of resazomycins.




How to Cite

Souder, K., Whaby, M., Hickman, J., Primerano, D., Denvir, J., & Schmitt, D. (2021). Contribution of Francisella tularensis FTL_1306 (dipA) in resazomycin susceptibility. Proceedings of the West Virginia Academy of Science, 93(1). Retrieved from