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首页> 外文期刊>Applied Microbiology >Dynamics of Mycobacteriophage-Mycobacterial Host Interaction: Evidence for Secondary Mechanisms for Host Lethality
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Dynamics of Mycobacteriophage-Mycobacterial Host Interaction: Evidence for Secondary Mechanisms for Host Lethality

机译：分枝杆菌-分枝杆菌宿主相互作用的动力学：宿主致死性二级机制的证据

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Mycobacteriophages infect mycobacteria, resulting in their death. Therefore, the possibility of using them as therapeutic agents against the deadly mycobacterial disease tuberculosis (TB) is of great interest. To obtain better insight into the dynamics of mycobacterial inactivation by mycobacteriophages, this study was initiated using mycobacteriophage D29 and Mycobacterium smegmatis as the phage-host system. Here, we implemented a goal-oriented iterative cycle of experiments on one hand and mathematical modeling combined with Monte Carlo simulations on the other. This integrative approach lends valuable insight into the detailed kinetics of bacterium-phage interactions. We measured time-dependent changes in host viability during the growth of phage D29 in M. smegmatis at different multiplicities of infection (MOI). The predictions emerging out of theoretical analyses were further examined using biochemical and cell biological assays. In a phage-host interaction system where multiple rounds of infection are allowed to take place, cell counts drop more rapidly than expected if cell lysis is considered the only mechanism for cell death. The phenomenon could be explained by considering a secondary factor for cell death in addition to lysis. Further investigations reveal that phage infection leads to the increased production of superoxide radicals, which appears to be the secondary factor. Therefore, mycobacteriophage D29 can function as an effective antimycobacterial agent, the killing potential of which may be amplified through secondary mechanisms.
机译：分枝杆菌感染分枝杆菌，导致其死亡。因此，将它们用作治疗致命的分枝杆菌结核病（TB）的治疗剂的可能性备受关注。为了更好地了解分枝杆菌噬菌体灭活的动力学，本研究以分枝杆菌噬菌体D29和耻垢分枝杆菌作为噬菌体宿主系统启动。在这里，我们一方面实现了实验的面向目标的迭代循环，另一方面实现了结合蒙特卡洛模拟的数学建模。这种综合方法为细菌-噬菌体相互作用的详细动力学提供了宝贵的见识。我们测量了在不同感染复数（MOI）下，耻垢分枝杆菌中噬菌体D29生长期间宿主活力的时间依赖性变化。从理论分析中得出的预测结果将使用生化和细胞生物学分析进行进一步检查。在允许发生多轮感染的噬菌体-宿主相互作用系统中，如果认为细胞裂解是唯一的细胞死亡机制，则细胞计数下降的速度将超过预期。这种现象可以通过考虑细胞裂解中的次要因素来解释。进一步的研究表明，噬菌体感染导致超氧化物自由基的产生增加，这似乎是次要因素。因此，分枝杆菌噬菌体D29可以用作有效的抗分枝杆菌剂，其杀伤潜力可通过二级机制得到增强。

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