关键词: Klebsiella aerogenes Bacteriophage Flagellum-dependent Jumbo phage Phage resistance Phage therapy Phage-binding receptor

Mesh : Bacteriophages / genetics classification isolation & purification physiology Genome, Viral Flagella / virology genetics Enterobacter aerogenes / virology genetics Host Specificity Whole Genome Sequencing Myoviridae / genetics isolation & purification classification physiology

来  源:   DOI:10.1186/s12866-024-03387-1   PDF(Pubmed)

Abstract:
BACKGROUND: Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages.
RESULTS: A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360 kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.
CONCLUSIONS: fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.
摘要:
背景:产气克雷伯菌是一种机会性病原体,可引起多种感染。由于抗生素耐药性问题日益严重,需要新型抗生素和对抗细菌感染的策略.宿主特异性噬菌体是细菌的天敌,并且可以用于噬菌体疗法作为针对细菌感染的替代治疗形式。巨型噬菌体被定义为基因组大于200kb的噬菌体。与小型噬菌体相比,大型噬菌体的研究相对较少。
结果:一种新型噬菌体,fENko-Kae01是从商业噬菌体混合物中分离的。基因组分析显示,fENko-Kae01是一种裂解性巨型噬菌体,其基因组为360kb,编码578个预测基因。没有鉴定出高度相似的噬菌体基因组,fENko-Kae01可能是一个全新的属代表。没有与溶源性生命周期相关的已知基因,细菌毒力,或鉴定了抗生素抗性。噬菌体具有病毒形态和狭窄的宿主范围。噬菌体抗性细菌突变体在噬菌体选择下出现。全基因组测序显示,鞭毛的生物发生在四个突变体中受到影响,并且在运动性测定中证实了功能鞭毛的缺乏。此外,噬菌体fENKo-Kae01未能吸附在非活动突变体上,表明细菌鞭毛是噬菌体结合受体。
结论:fENko-Kae01是一种新型巨型噬菌体,被认为对噬菌体治疗是安全的。fENko-Kae01使用鞭毛作为噬菌体结合受体,可能代表一个全新的属。
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