Amixicile targets anaerobic bacteria within the oral microbiome.
Amixicile targets anaerobic bacteria within the oral microbiome.
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DOI：
10.1016/j.job.2019.10.004
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发表时间：
2019-12
影响因子：
2.4
通讯作者：
Lewis JP
中科院分区：
文献类型：
--
作者：
Gui Q;Hoffman PS;Lewis JP
厌氧菌是牙周病的主要致病菌。然而，到目前为止，旨在减少这些病原体的靶向治疗尚未得到广泛实施。我们之前已经报道了一种新型抗菌剂，阿米西林，它通过抑制主要厌氧代谢酶丙酮酸铁氧还蛋白氧化还原酶(PFOR)的功能来靶向厌氧菌，而不影响耐氧微生物。它能有效地抑制口腔厌氧菌在单一培养和混合体外混合培养中的生长，但在体内类似条件下的活性仍有待确定。在这里，我们使用体外口腔微生物组结合后基因组测序来扩展我们的研究，以确定阿米昔利治疗对微生物组组成的影响，并将其与甲硝唑进行比较。结果表明，在复合微生物群中，厌氧菌受到选择性抑制，而耐氧菌如链球菌、克雷伯氏菌、奈瑟氏菌和罗氏菌的生长不受影响。Veillonella是我们体外微生物组中最丰富的厌氧菌属，我们观察到它的生长完全被抑制。此外，其他厌氧菌梭杆菌和普雷沃特氏菌的生长也受到显著抑制。乳酸菌只有在高浓度的阿米西林才被抑制。值得注意的是，观察到与口腔微生物群相关的噬菌体，如噬菌体和肌病毒科的丰度发生了变化。总的来说，我们的数据扩展了到目前为止报道的阿米西林的抑制谱，并证明它抑制厌氧细菌，包括临床分离和实验室菌株。唾液微生物群由利用丙酮酸脱氢酶(PD)或其他机制的耐氧细菌和依赖于丙酮酸铁氧还蛋白氧化还原酶(PFOR)的厌氧细菌的混合物组成，丙酮酸脱羧酶(PFOR)是产生能量的主要代谢步骤。用阿米昔林治疗唾液微生物组，选择性地抑制依赖PFOR的细菌的生长，并将微生物组转换为含有与牙周健康相关的细菌的微生物组。
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 metabolic enzyme pyruvate ferredoxin oxidoreductase (PFOR), while not affecting aerotolerant organisms. It effectively inhibited the growth of oral anaerobes both in monocultures as well as in mixed in vitro mixed cultured however, amixicile’s activity in in vivo-like conditions remained to be established. 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, while the growth of aerotolerant ones, such as Streptococcus, Klebsiella, Neisseria, and Rothia is unaffected. Veillonella was the most abundant anaerobic genus in our ex vivo microbiome, and we observed complete inhibition of its growth. In addition, growth of other anaerobes, Fusobacterium and Prevotella, was significantly inhibited. Lactobacillus was inhibited only at high concentrations of amixicile. It is noteworthy that a change in abundance of bacteriophages, such as Siphoviridae and Myoviridae, associated with the oral microbiome was observed. Collectively, our data expand on the so far reported inhibitory spectrum of amixicile and demonstrates that it inhibits anaerobic bacteria, including both clinical isolates and laboratory strains. The salivary microbiome is composed of a mixture of aerotolerant bacteria utilizing pyruvate dehydrogenase (PD) or other mechanisms and anaerobic bacteria relying on pyruvate ferredoxin oxidoreductase (PFOR) for the decarboxylation of pyruvate; a major metabolic step in energy generation. Treatment of the salivary microbiome with amixicile selectively inhibits the growth of bacteria relying on PFOR and converts the microbiome to one containing bacteria associated with periodontal health.
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影响因子：
15.5
作者：
Edlund A;Yang Y;Hall AP;Guo L;Lux R;He X;Nelson KE;Nealson KH;Yooseph S;Shi W;McLean JS
通讯作者：
McLean JS
影响因子：
14.9
作者：
Markowitz VM;Chen IM;Palaniappan K;Chu K;Szeto E;Pillay M;Ratner A;Huang J;Woyke T;Huntemann M;Anderson I;Billis K;Varghese N;Mavromatis K;Pati A;Ivanova NN;Kyrpides NC
通讯作者：
Kyrpides NC
影响因子：
--
作者：
Araki, H;Kuriyama, T;Karasawa, T
通讯作者：
Karasawa, T
影响因子：
3.7
作者：
Byrne, D. P.;Potempa, J.;Smalley, J. W.
通讯作者：
Smalley, J. W.
DOI：
10.1038/s41579-018-0089-x
发表时间：
2018-12
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Lamont RJ;Koo H;Hajishengallis G
通讯作者：
Hajishengallis G