Hodyra-Stefaniak Katarzyna, Miernikiewicz Paulina, Drapała Jarosław, Drab Marek, Jończyk-Matysiak Ewa, Lecion Dorota, Kaźmierczak Zuzanna, Beta Weronika, Majewska Joanna, Harhala Marek, Bubak Barbara, Kłopot Anna, Górski Andrzej, Dąbrowska Krystyna
Bacteriophage Laboratory, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland.
Institute of Computer Science, Wrocław University of Technology, Wyb. Wyspiańskiego 27, 50-370, Wrocław, Poland.
Sci Rep. 2015 Oct 6;5:14802. doi: 10.1038/srep14802.
Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies, and serum complement were identified by direct testing and by high-resolution fluorescent microscopy. We accommodated the experimental data into a mathematical model. We propose a universal schema of innate and adaptive immunity impact on phage pharmacokinetics, based on the results of our numerical simulations. We found that the mammalian-host response to infecting bacteria causes the concomitant removal of phage from the system. We propose the notion that this effect as an indirect pathway of phage inhibition by bacteria with significant relevance for the clinical outcome of phage therapy.
新出现的细菌抗生素耐药性使噬菌体成为治疗细菌感染的一种治疗选择而备受关注。对抗细菌的噬菌体例子比比皆是。然而，尽管在体外对抗菌活性进行了仔细测试，但治疗失败仍很常见。我们研究了噬菌体抗菌效力在体内的免疫反应。通过直接测试和高分辨率荧光显微镜鉴定了吞噬细胞、抗体和血清补体的抗噬菌体活性。我们将实验数据纳入一个数学模型。基于我们的数值模拟结果，我们提出了先天免疫和适应性免疫对噬菌体药代动力学影响的通用模式。我们发现哺乳动物宿主对感染细菌的反应会导致噬菌体从系统中随之被清除。我们提出这一效应是细菌抑制噬菌体的间接途径，这与噬菌体治疗的临床结果具有重要相关性。
