中文摘要：铜绿假单胞菌是一种条件致病菌，可引起免疫功能低下和慢性囊性纤维化(CF)患者的医院感染。本文鉴定了两种新分离的具有不同宿主谱的假单胞菌噬菌体phi PA01和phi-PA02，并将其与抗生素联合用于铜绿假单胞菌，以说明噬菌体混合物与抗生素联合治疗铜绿假单胞菌感染的可能性。噬菌体phi PA01（66220bp）和phi-PA02（279095 bp）分别属于Pbunalikevirus 和Phikzlikevirus属。它们的基因组中没有发现毒力或溶源性相关基因，因此用于噬菌体治疗很安全。本研究制备了它们各自的噬菌体抗性菌株来研究两个噬菌体之间的交叉抗性，发现抗phi PA01菌株对phi PA02有轻微的交叉抗性，而抗phi PA02菌株对phi PA01仍然敏感。抗PA01菌株在第5轮(R5-PA01R)出现了对phi PA02的交叉抗性，揭示出磷酸葡萄糖转换酶(algC)的移码突变，该突变对核心脂多糖(LPS)的合成具有重要意义。敲除algC对两种噬菌体都有抗性。δalgC的互补作用恢复了噬菌体的传染性，表明LPS为宿主受体。与单个噬菌体(8e9h)相比，噬菌体混合物抑制铜绿假单胞菌生长的时间更长(20h)。此外，应用环丙沙星和美罗培南噬菌体混合物对铜绿假单胞菌的抑制作用长达96h。可见，phi PA01和phi PA02作为噬菌体混合物与抗生素联合治疗铜绿假单胞菌具有潜在的应用价值。
外文摘要：Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial disease among immunocompromised and chronic cystic fibrosis (CF) patients. We characterized two newly isolated Pseudomonas phages, phi PA01 and phi PA02, with different host spectra, and examined their effect as a cocktail with antibiotics against P. aeruginosa, to indicate the possibility of combining a phage cocktail and antibiotics in treating pseudomonal infection. Phages phi PA01 (66,220 bp) and phi PA02 (279,095 bp) belong to the genus Pbunalikevirus and Phikzlikevirus, respectively. No virulence or lysogenic associated gene was found in their genomes, thus they are potentially safe for phage therapy. We generated respective phage-resistant strains to investigate cross-resistance between two phages. Slight cross-resistance to phi PA02 in phi PA01-resistant strain was observed, while phi PA02-resistant strain remained susceptible to phi PA01. A phi PA01 resistant strain that was cross-resistant to phi PA02 appeared in round 5 (R5-PA01R), revealed frameshift mutation in phosphoglucomutase (algC), which is important for the synthesis of core lipopolysaccharide (LPS). Knockout of algC was resistant to both phages. Complementation of Delta algC restored phages' infectivity, suggesting that LPS as host receptor. Phage cocktail suppressed the growth of P. aeruginosa for longer (20 h) hour compared with single phage (8e9 h), further suggesting their potential to be used as a phage cocktail. Furthermore, application of the phage cocktail with ciprofloxacin (0.25 mu g/ ml) and meropenem (2 mu g/ml), managed to suppress the growth of P. aeruginosa up to 96 h. Our results show the potential application of phi PA01 and phi PA02 as phage cocktail together with antibiotics for treatment of P. aeruginosa.
 
外文关键词：Antibiotics; Phage therapy; Phikzlikevirus; Pbunalikevirus; Pseudomonas aeruginosa
作者：Ong, SP；Azam, AH；Sasahara, T；Miyanaga, K；Tanji, Y
作者单位：Tokyo Inst Technol；Jichi Med Univ
期刊名称：JOURNAL OF BIOSCIENCE AND BIOENGINEERING
期刊影响因子：2.366
出版年份：2020
出版刊次：6
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