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模拟抗菌治疗情况下噬菌体载量及给药时间的测定

Determination of phage load and administration time in simulated occurrences of antibacterial treatments.

作者信息

Plunder Steffen, Burkard Markus, Lauer Ulrich M, Venturelli Sascha, Marongiu Luigi

机构信息

Department of Mathematics, University of Vienna, Vienna, Austria.

Department of Nutritional Biochemistry, University of Hohenheim, Stuttgart, Germany.

出版信息

Front Med (Lausanne). 2022 Oct 28;9:1040457. doi: 10.3389/fmed.2022.1040457. eCollection 2022.

Abstract

The use of phages as antibacterials is becoming more and more common in Western countries. However, a successful phage-derived antibacterial treatment needs to account for additional features such as the loss of infective virions and the multiplication of the hosts. The parameters critical inoculation size ( ) and failure threshold time ( ) have been introduced to assure that the viral dose ( ) and administration time ( ) would lead to the extinction of the targeted bacteria. The problem with the definition of and is that they are non-linear equations with two unknowns; thus, obtaining their explicit values is cumbersome and not unique. The current study used machine learning to determine and for an effective antibacterial treatment. Within these ranges, a Pareto optimal solution of a multi-criterial optimization problem (MCOP) provided a pair of and to facilitate the user's work. The algorithm was tested on a series of microbial consortia that described the outgrowth of a species at high cell density by another species initially present at low concentration. The results demonstrated that the MCOP-derived pairs of and could effectively wipe out the bacterial target within the context of the simulation. The present study also introduced the concept of mediated phage therapy, where targeting booster bacteria might decrease the virulence of a pathogen immune to phagial infection and highlighted the importance of microbial competition in attaining a successful antibacterial treatment. In summary, the present work developed a novel method for investigating phage/bacteria interactions that can help increase the effectiveness of the application of phages as antibacterials and ease the work of microbiologists.

摘要

在西方国家,噬菌体作为抗菌剂的应用越来越普遍。然而,成功的噬菌体衍生抗菌治疗需要考虑其他因素,如感染性病毒粒子的损失和宿主的繁殖。为确保病毒剂量( )和给药时间( )能导致目标细菌灭绝,引入了关键接种量( )和失效阈值时间( )这两个参数。 和 的定义问题在于它们是含有两个未知数的非线性方程;因此,获取其明确值既繁琐又不唯一。当前研究利用机器学习来确定有效抗菌治疗的 和 。在这些范围内,多准则优化问题(MCOP)的帕累托最优解提供了一对 和 ,以方便用户工作。该算法在一系列微生物群落上进行了测试,这些群落描述了一种最初以低浓度存在的物种在高细胞密度下另一种物种的生长情况。结果表明,MCOP得出的 和 对在模拟环境中能有效消灭细菌目标。本研究还引入了介导噬菌体疗法的概念,即靶向增强细菌可能会降低对噬菌体感染免疫的病原体的毒力,并强调了微生物竞争在实现成功抗菌治疗中的重要性。总之,本研究开发了一种研究噬菌体/细菌相互作用的新方法,有助于提高噬菌体作为抗菌剂应用的有效性,并减轻微生物学家的工作负担。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f97f/9650209/2f2b156f72e7/fmed-09-1040457-g001.jpg

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