The Second Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, 450002, China.
Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450002, China; The Key Laboratory of Pathogenic Microbes &Antimicrobial Resistance Surveillance of Zhengzhou, Zhengzhou, 450002, China; Henan Engineering Research Center for Identification of Pathogenic Microbes, Zhengzhou, 450002, China; Henan Provincial Key Laboratory of Antibiotics-Resistant Bacterial Infection Prevention & Therapy with Traditional Chinese Medicine, Zhengzhou, 450002, China.
Virus Res. 2023 Oct 2;335:199184. doi: 10.1016/j.virusres.2023.199184. Epub 2023 Aug 2.
Pseudomonas aeruginosa is a clinically common conditionally pathogenic bacterium, and the abuse of antibiotics has exacerbated its drug resistance in recent years. This has resulted in extensive reports about the usage of Pseudomonas aeruginosa phage as a novel antibacterial drug. In this study, we isolated a novel phage HZ2201 with a broad lytic spectrum. The lytic rate of this phage against Pseudomonas aeruginosa reached 78.38% (29/37), including 25 multi-drug- and carbapenem-resistant Pseudomonas aeruginosa strains. Transmission electron microscopy revealed that phage HZ2201 belongs to the class Caudoviricetes. Biological characterization showed that phage HZ2201 had an latent period of 40 min, a lytic period of 20 min, and a burst size of 440 PFU/cell, with improved tolerance to temperature and pH. Considering genomic analysis, the HZ2201 genome was a circular double-stranded DNA with a size of 45,431 bp and a guanine-cytosine (G + C) content of 52.16%, and contained 3 tRNAs. 27 of the 74 open reading frames (ORFs) annotated by the Rapid Annotation using Subsystem Technology (RAST) tool could be matched to the genomes of known functions, and no genes related to virulence and antibiotic resistance were found. The phylogenetic tree suggests that phage HZ2201 is highly related to the phage ZCPS1 and PaP3, and ORF57 and ORF17 are predicted to encode a holin and an endolysin, respectively. Cell lysis by HZ2201 proceeds through the holin-endolysin system, suggesting that it is a novel phage. Additionally, we demonstrated that phage HZ2201 has a high inhibitory capacity against Pseudomonas aeruginosa biofilms. The results of our study suggest that phage HZ2201 is a novel potential antimicrobial agent for treating drug-resistant Pseudomonas aeruginosa infection.
铜绿假单胞菌是一种临床上常见的条件致病菌，近年来抗生素的滥用使其耐药性加剧。这导致了广泛报道使用铜绿假单胞菌噬菌体作为新型抗菌药物。在本研究中，我们分离到一种新型噬菌体 HZ2201，具有广泛的裂解谱。该噬菌体对铜绿假单胞菌的裂解率达到 78.38%（29/37），包括 25 株多药耐药和碳青霉烯类耐药铜绿假单胞菌。透射电子显微镜显示噬菌体 HZ2201 属于长尾病毒科。生物学特性表明，噬菌体 HZ2201 的潜伏期为 40 分钟，裂解期为 20 分钟，爆发量为 440PFU/细胞，对温度和 pH 值具有更好的耐受性。考虑到基因组分析，HZ2201 基因组是一个大小为 45431bp 的圆形双链 DNA，G+C 含量为 52.16%，含有 3 个 tRNA。通过快速基因组分析系统（RAST）注释，74 个开放阅读框（ORFs）中的 27 个可以与已知功能的基因组匹配，并且没有发现与毒力和抗生素耐药性相关的基因。系统发育树表明噬菌体 HZ2201 与噬菌体 ZCPS1 和 PaP3 高度相关，推测 ORF57 和 ORF17 分别编码一个溶孔蛋白和一个内溶素。HZ2201 通过溶孔蛋白-内溶素系统裂解细胞，提示它是一种新型噬菌体。此外，我们证明噬菌体 HZ2201 对铜绿假单胞菌生物膜具有高抑制能力。我们的研究结果表明，噬菌体 HZ2201 是一种治疗耐药铜绿假单胞菌感染的新型潜在抗菌剂。
