Lipophilic Prodrugs of FR900098 Are Antimicrobial against Francisella novicida In Vivo and In Vitro and Show GlpT Independent Efficacy
Figure 3
Susceptibility of F. novicida glpT mutants to antibiotics.
Fosmidomycin, FR900098, compound 1, and compound 2 were tested at concentrations of 200 µg/ml. F. novicida glpT mutants were resistant to fosmidomycin and partially resistant to FR900098, but not at all resistant to compound 1. Compound 2 was less effective against the glpT mutant than wild-type F. novicida. Percent inhibition was calculated by comparing OD600 between treated and untreated wells. Fosmidomycin inhibited 99.6±0.2% of wild-type F. novicida, but did not inhibit the growth of the glpT mutant at all. FR900098 inhibited 97.1±0.8% of F. novicida, but only 55±5% of the glpT mutant. Compound 1 inhibited 100% of the growth of both wild-type F. novicida and the glpT mutant. Compound 2 inhibited 27±14% of F. novicida, and 11±7% of the glpT mutant.