Amixicile inhibits anaerobic bacteria within salivary microbiome

Anaerobic bacteria are the major causative agents of periodontal disease, however, so far targeted therapy aimed at reducing those pathogens has not been widely implemented. We have previously reported on a novel antimicrobial, amixicile that targets anaerobic bacteria through inhibition of the function of the major anaerobic enzyme pyruvate ferredoxin oxidoreductase (PFOR), while having no effect on aerobic bacteria. That studies have shown that amixicile effectively inhibited growth of oral anaerobes both in monocultures as well as in mixed in vitro microbiomes. Here we expand our study using an ex vivo oral microbiome combined with metagenomic sequencing to determine the effect of amixicile treatment on the composition of the microbiome and compare it to that of metronidazole. Our results show that in the complex microbiomes anaerobic bacteria are selectively inhibited. Veillonella spp was the most abundant anaerobic species in our ex vivo microbiome and we did observe complete inhibition of growth of the bacterium. Also, Fusobacterium spp and Prevotella spp were significantly inhibited. Lactobacillus spp were inhibited at high concentrations of amixicile but not at a lower one. The inhibition profile observed in this study was verified using monoculture growth studies. Collectively, our data expands the so far reported inhibitory spectrum of amixicile and demonstrates that it inhibits anaerobic bacteria including both clinical isolates and laboratory strains.