Lytic and genomic properties of spontaneous host-range Kayvirus mutants prove their suitability for upgrading phage therapeutics against staphylococci
Lytic and genomic properties of spontaneous host-range Kayvirus mutants prove their suitability for upgrading phage therapeutics against staphylococci
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DOI：
10.1038/s41598-019-41868-w
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发表时间：
2019-04-02
影响因子：
4.6
通讯作者：
Doskar, Jiri
中科院分区：
文献类型：
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作者：
Botka, Tibor;Pantucek, Roman;Doskar, Jiri
裂解性噬菌体是抗细菌感染的有价值的治疗剂。人们一直在努力获得新的噬菌体，以提高噬菌体制剂对新出现的噬菌体抗性菌株的有效性。在这里，我们描述了Kayvirus 812的自发宿主范围突变体的基因组多样性。在抗噬菌体金黄色葡萄球菌菌株上分离出五种突变体噬菌斑。噬菌体812衍生的突变体的宿主范围比野生型高42%，测定了一组186个耐甲氧西林的S。金黄色葡萄球菌菌株代表全球循环的人类和牲畜相关克隆。比较基因组学显示，单核苷酸多态性从父母的噬菌体812人口被固定在下一步的突变体，主要是在基因的尾巴和基板组件，和收购点突变导致不同的受体结合蛋白的噬菌体突变体。结果表明，大量的基因组变化与直接重复序列的重排或内含子丢失有关，表现出最高裂解活性的突变体的宿主接管区、末端基因组区域或内溶素基因发生了改变，这暗示了细菌克服耐药性的多种机制。基因组数据显示，Kayvirus自发突变体不含不需要的基因，并且它们的裂解性质证明了它们适用于快速更新的噬菌体治疗剂。
Lytic bacteriophages are valuable therapeutic agents against bacterial infections. There is continual effort to obtain new phages to increase the effectivity of phage preparations against emerging phage-resistant strains. Here we described the genomic diversity of spontaneous host-range mutants of kayvirus 812. Five mutant phages were isolated as rare plaques on phage-resistant Staphylococcus aureus strains. The host range of phage 812-derived mutants was 42% higher than the wild type, determined on a set of 186 methicillin-resistant S. aureus strains representing the globally circulating human and livestock-associated clones. Comparative genomics revealed that single-nucleotide polymorphisms from the parental phage 812 population were fixed in next-step mutants, mostly in genes for tail and baseplate components, and the acquired point mutations led to diverse receptor binding proteins in the phage mutants. Numerous genome changes associated with rearrangements between direct repeat motifs or intron loss were found. Alterations occurred in host-takeover and terminal genomic regions or the endolysin gene of mutants that exhibited the highest lytic activity, which implied various mechanisms of overcoming bacterial resistance. The genomic data revealed that Kayvirus spontaneous mutants are free from undesirable genes and their lytic properties proved their suitability for rapidly updating phage therapeutics.