Abstract
Periodontitis is an inflammatory condition triggered by selected oral microbiota; thus treatment strategies should be aimed at reducing the abundance of the pathogenic bacteria. An obstacle to preclinical testing of such strategies is the availability of reliable animal models. Here, a non-human primate (NHP), Macaca mulatta, was used to examine the effectiveness of a novel antimicrobial, amixicile, which inhibits pyruvate–ferredoxin oxidoreductase (PFOR) present in anaerobic bacteria. Animals were assessed for their periodontal health, including radiography, clinical attachment loss (CAL), presence of plaque (PI), bleeding on probing (BOP) and pocket depth (PD), and sampled for saliva, gingival crevicular fluid (GCF), and subgingival plaque to determine their baseline clinical status. Amixicile was then administered for 2 weeks (40 mg/kg/day) and the animals were monitored for periodontal health immediately after the antibiotic treatment, then at 1 month-, 3 months-, and 6-months posttreatment. Microbial species present in plaque and saliva were determined through 16S rDNA sequencing. Baseline assessment of the microbiome has shown a significant proportion of bacteria belonging to the Streptococcus, Haemophilus, Porphyromonas, Gemella, and Fusobacterium genera. The abundance of Porphyromonas and Fusobacterium was reduced following treatment with amixicile, whereas that of Escherichia, Haemophilus, and Gemella were elevated. CAL, PD, and BOP were also significantly reduced following the treatment. In conclusion, the NHP model proves useful for preclinical studies of strategies targeting selected members of the oral microbiome. We show that amixicile reduces the levels of anaerobic bacteria under in vivo conditions, correlating with a reduction in CAL, PD, and BOP, thus validating its usefulness as an antimicrobial strategy.
Highlights
Rodent models provide useful information for many of the oral bacteria–host interactions, they are inadequate to determine the efficacy of an antimicrobial agent to treat periodontitis in humans [1, 2]
We examined the efficacy of amixicile, a newly developed inhibitor of pyruvate ferredoxin oxidoreductase (PFOR), which is an enzyme critical for energy generation in anaerobic bacteria
The values for clinical attachment loss (CAL) in mm ranged: 0–5 at baseline, 0–4 posttreatment, 0–4 at 3 months, and 0–4 at 6 months. Both animals presented with pocket depth (PD) of 1–4 mm at the baseline exam with localized interproximal PD of 4 mm and localized slight radiographic bone loss which corresponds to mild periodontitis for non-human primate (NHP) [1]
Summary
Rodent models provide useful information for many of the oral bacteria–host interactions, they are inadequate to determine the efficacy of an antimicrobial agent to treat periodontitis in humans [1, 2]. Previous studies of amixicile have shown promising outcomes in specific inhibition in the growth of anaerobic bacteria in both in vitro and ex vivo microbiomes [3, 4]. Suitability of amixicile was further supported by data showing its minimal effect on gut microbiota and its ability to concentrate at sites with inflammation [5, 6]. All these characteristics suggest that amixicile may be an antimicrobial for the treatment of periodontitis. We tested the suitability of the NHP model with naturally occurring periodontitis to examine the efficacy of amixicile as a potential treatment for periodontal disease
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