Targeting antibiotic resistant bacteria with phages reduces bacterial density in an insect host
Targeting antibiotic resistant bacteria with phages reduces bacterial density in an insect host
复制标题
用噬菌体靶向抗生素抗性细菌可降低昆虫宿主中的细菌密度
DOI：
10.1101/493718
复制
发表时间：
2018
期刊：
影响因子：
--
通讯作者：
B. Raymond
中科院分区：
文献类型：
--
作者：
L. Mikonranta;A. Buckling;M. Jalasvuori;B. Raymond
随着抗生素耐药性变得越来越难以控制，噬菌体疗法越来越受到临床医生的关注。然而，噬菌体治疗的临床试验和动物模型研究仍然很少，疗效结果也各不相同。最近的研究表明，将传统抗菌药物与噬菌体结合使用可能会产生理想的协同效应，从而阻碍耐药性的进化。在这里，我们提出了一种新型昆虫肠道模型，用于研究噬菌体与抗生素相互作用的系统，其中抗生素耐药性最初以非常低的频率存在，并且噬菌体专门针对具有耐药性的细胞。我们证明，虽然噬菌体疗法不能降低抗生素阳性选择期间群体中目标细菌的频率，但它通过降低耐药细胞的总体负荷来减轻抗生素诱导的繁殖。与体外相比，高度结构化的肠道环境对噬菌体和抗生素动力学都有药代动力学影响：抗生素不会减少细菌总量，这表明肠道菌群从非耐药菌群到耐药菌群的简单转换，成本很低。结果表明，使用噬菌体作为针对抗生素耐药性肠道感染的辅助手段具有中等潜力，并质疑体外推论的有用性。
Phage therapy is attracting growing interest among clinicians as antibiotic resistance continues becoming harder to control. However, clinical trials and animal model studies on bacteriophage treatment are still scarce and results on the efficacy vary. Recent research suggests that using traditional antimicrobials in concert with phage could have desirable synergistic effects that hinder the evolution of resistance. Here, we present a novel insect gut model to study phage-antibiotic interaction in a system where antibiotic resistance initially exists in very low frequency and phage specifically targets the resistance bearing cells. We demonstrate that while phage therapy could not reduce the frequency of target bacteria in the population during positive selection by antibiotics, it alleviated the antibiotic induced blooming by lowering the overall load of resistant cells. The highly structured gut environment had pharmacokinetic effects on both phage and antibiotic dynamics compared to in vitro: antibiotics did not reduce the overall amount of bacteria, demonstrating a simple turnover of gut flora from non-resistant to resistant population with little cost. The results imply moderate potential for using phage as an aid to target antibiotic resistant gut infections, and question the usefulness of in vitro inferences.