Nourseothricin as a novel therapeutic agent against Neisseria gonorrhoeae: in vitro and in vivo evaluations using Galleria mellonella-a pilot study

Neisseria gonorrhoeae has developed resistance to multiple antibiotics, making the search for novel antimicrobial agents essential. This pilot study evaluates the in vitro and in vivo efficacy of nourseothricin, a streptothricin family antibiotic mixture primarily composed of streptothricin F, against N. gonorrhoeae, a previously unexplored therapeutic option. The minimum inhibitory concentrations (MICs) of nourseothricin were determined using the agar dilution method on a panel of N. gonorrhoeae strains, including multidrug-resistant isolates. The in vivo efficacy was assessed using the Galleria mellonella infection model, where larvae were infected with N. gonorrhoeae and treated with varying concentrations of nourseothricin. Survival rates were compared to those of ceftriaxone-treated and untreated control groups. Nourseothricin inhibited the growth of all tested N. gonorrhoeae strains, with MIC values ranging from 16 to 32 µg/mL, independent of resistance to ceftriaxone, ciprofloxacin, or azithromycin. In vivo, treatment with nourseothricin significantly improved larval survival compared to the untreated control group ( P < 0.01). The highest survival rate was observed with a 32 µg/mL dose, comparable to that of ceftriaxone-treated groups. Nourseothricin exhibited in vitro activity against N. gonorrhoeae, including multidrug-resistant strains. The in vivo results, obtained in a Galleria mellonella larval model, suggest that nourseothricin may warrant further investigation as a candidate compound for the treatment of gonorrhea, although its clinical potential remains to be evaluated in mammalian systems.

IMPORTANCE

The emergence of multidrug-resistant Neisseria gonorrhoeae has made the development of new treatments a critical priority. This study is the first to evaluate the in vivo efficacy of nourseothricin against N. gonorrhoeae, demonstrating its activity even against resistant strains. In addition to its in vitro efficacy, treatment with nourseothricin improved survival in an in vivo infection model, suggesting its potential as a therapeutic option. Given the increasing limitations of existing antibiotics, these findings support further investigation into nourseothricin as a candidate for future gonorrhea treatment.