Periodontitis is an inflammatory disease of the oral cavity induced by anaerobic bacteria, that remains to be the primary cause of tooth loss in adults worldwide. Finding an anti-microbial therapeutic to selectively target periodontal pathogens has proven to be difficult, and current treatment modalities only provide a transient benefit. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate, a critical step in metabolism. Our study aimed to evaluate the efficacy of amixicile in inhibiting the growth of bacteria harvested from the complex sub-gingival biofilm of patients with chronic periodontitis. We hypothesize that amixicile will selectively inhibit pathogenic anaerobic bacteria collected from patients, with the same efficacy as metronidazole, the current accepted treatment modality. Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence of amixicile and metronidazole and the growth was compared to that of bacteria grown in the absence of the antimicrobials. Following 24 hour incubation, bacterial DNA was isolated and bacterial quantity was evaluated by quantitative PCR (qPCR) using primers specific for 12 bacterial species: P. gingivalis (Pg), P. intermedia (Pi), F.nucleatum (Fn), S.gordonii (Sg), S. anginosus (Sa), V. atypical (Va), L. acidophilus (La), A.actinomycetemcomitans (Aa), T.denticola (Td), S.mutans (Sm), S.sanguis (Ss), and 16s. Individual qPCR runs were combined to represent an overall average of CT value differences. Amixicile treatment groups exhibited statistical significant reductions (PP. intermedia, F. nucleatum and Veillonella atypical. When comparing amixicile to metronidazole, amixicile performed with similar efficacy with the largest effect seen for PFOR bacteria. Our conclusion supports amixicile as a potent inhibitor of anaerobic bacteria, and could be a potential new therapeutic antimicrobial in the treatment of periodontal disease

Periodontitis is a chronic inflammatory disease caused by pathogenic bacteria residing in a complex biofilm within a susceptible host. Amixicile is a non-toxic, readily bioavailable novel antimicrobial that targets strict anaerobes through inhibition of the activity of Pyruvate Ferredoxin Oxidoreductase (PFOR), a major enzyme mediating oxidative decarboxylation of pyruvate. Our study aimed to evaluate the efficacy of amixicile, when compared to metronidazole, in inhibiting the growth of bacteria present in a microbiome harvested from patients with chronic periodontitis. Plaque samples were harvested from patients with severe chronic periodontitis and cultured under anaerobic conditions. The microbiomes were grown in the presence of amixicile and metronidazole and the growth was compared to that of bacteria grown in the absence of the antimicrobials. Following 24 hour growth the bacterial DNA was analyzed using quantitative PCR (qPCR) using primers specific for 12 bacterial species: P. gingivalis (Pg), P. intermedia (Pi), F.nucleatum (Fn), S.gordonii (Sg), S. anginosus (Sa), V. atypical (Va), L. acidophilus (La), A.actinomycetemcomitans (Aa), T.denticola (Td), S.mutans (Sm), and S.sanguis (Ss). Both drug treatment groups yielded a statistical significant reduction for several anaerobic bacteria: Pi (P

Periodontal disease (PD) is a polymicrobial infection characterized by inflammation of the gingiva, alveolar bone resorption, and tooth loss (edentulism). Treponema denticola along with Porphyromonas gingivalis and Tannerella forsythia are among the “Red Complex” and are main etiological agents in PD. Treponemes are a member of the Spirochaeta phylum and are obligate anaerobes, that express pyruvate ferredoxin oxidoreductase (PFOR). The enzyme catalyzes the oxidation of pyruvate to acetyl-CoA and reduced ferredoxin. Amixicile is a novel bacteriostatic derivative of nitazoxanide and an inhibitor of PFOR. In light of the fact that Treponemes express PFOR, this study was conducted to investigate the susceptibility of oral Treponemes to AMX. All oral Treponemes tested were susceptible to AMX and the MIC values were determined ranging of 1.5-4.5 μg mL-1 for an initial starting cell concentration of 1.9x106 cells mL-1. Other potentially therapeutic effects for AMX for T. denticola were investigated: motility, hydrogen sulfide production, and serum sensitivity. AMX reduced overall spirochete motility by 50% at sub-MIC concentrations. There was a dose dependent decrease in H2S production in T. denticola at sub-MIC and MIC values. Furthermore, prior exposure of AMX led to increases in serum sensitivity. Taking into account the fact that other periodontal red complex bacteria express PFOR, AMX could serve as a new selective adjunctive treatment for periodontal disease.