Determining the role of the pilD gene in Francisella tularensis susceptibility to resazomycins.

Abstract

Antimicrobial resistant strains (AMRs) of bacteria have become such a severe worldwide issue that the United Nations General assembly met in 2016 to discuss the topic of AMRs. Due to the increase in the number of antibiotic-resistant strains, new therapeutics against AMRs must be developed.  Resazomycins are resazurin-based compounds that exhibit antimicrobial activity against F. tularensis as well as other Gram-negative bacteria including N. gonorrheae. The mode of action of these antibiotics is not understood.  Approximately half of forty-eight resazurin-resistant F. tularensis isolates had a mutation in the genes FTL_0959 (pilD) and FTL_1306 (dipA). The objective of this project is to determine how pilD affects F. tularensis susceptibility to resazomycins. In F. tularensis, pilD encodes for the cytoplasmic membrane peptidase responsible for processing the prepilin subunits in type IV pilin assembly proteins. We are currently working to generate a pilD null deletion mutant using standard molecular genetic techniques. We will first confirm the sensitivity of the pilD deletion mutant to resazomycins. Understanding the role of pilD in resazomycin susceptibility would facilitate further development of these compounds as potential treatments for tularemia and gonorrhea.