Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy.
Non-human Primate Macaca mulatta as an Animal Model for Testing Efficacy of Amixicile as a Targeted Anti-periodontitis Therapy.
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DOI：
10.3389/froh.2021.752929
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发表时间：
2021
影响因子：
--
通讯作者：
Lewis JP
中科院分区：
文献类型：
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作者：
Gui Q;Lyons DJ;Deeb JG;Belvin BR;Hoffman PS;Lewis JP
牙周炎是一种由选定的口腔微生物区系引发的炎症状况；因此，治疗策略应旨在减少致病菌的丰度。这种策略的临床前试验的一个障碍是可靠的动物模型的可用性。在这里，非人灵长类(NHP)猕猴被用来检测一种新型抗菌剂阿米西林的有效性，它抑制厌氧细菌中存在的丙酮酸-铁氧还蛋白氧化还原酶(PFOR)。对动物的牙周健康进行评估，包括X线片、临床附着丧失(CAL)、菌斑存在(PI)、探诊出血(BOP)和牙袋深度(PD)，并采集唾液、牙龈沟液(GCF)和龈下菌斑以确定其基线临床状态。然后给予阿米西林2周(40 mg/kg/天)，在抗生素治疗后立即监测动物的牙周健康，然后在治疗后1个月、3个月和6个月监测牙周健康。通过16S rDNA测序确定菌斑和唾液中的微生物种类。对微生物组的基线评估显示，有相当大比例的细菌属于链球菌、嗜血杆菌、卟啉单胞菌、双胞菌和梭杆菌属。阿米西林处理后，卟啉单胞菌和梭杆菌的丰度降低，而大肠埃希菌、嗜血杆菌和双歧杆菌的丰度增加。治疗后CAL、PD和BOP也显著降低。总之，NHP模型被证明对于针对选定的口腔微生物组成员的策略的临床前研究是有用的。我们发现，在活体条件下，阿米西林降低了厌氧菌的水平，与CAL、PD和BOP的减少相关，从而验证了其作为抗菌策略的有效性。
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.