Institute of Medical Sciences, Tzu Chi University, No. 701, Sec. 3, Zhongyang Rd., Hualien 97004, Taiwan, ROC.
Department of Dentistry, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 707, Sec. 3, Zhongyang Rd., Hualien 97004, Taiwan, ROC.
Virus Res. 2023 Oct 2;335:199178. doi: 10.1016/j.virusres.2023.199178. Epub 2023 Aug 3.
Multiple drug-resistant (MDR) Pseudomonas aeruginosa commonly causes severe hospital-acquired infections. The gradual emergence of carbapenem-resistant P. aeruginosa has recently gained attention. A wide array of P. aeruginosa-mediated pathogenic mechanisms, including its biofilm-forming ability, limits the use of effective antimicrobial treatments against it. In the present study, we isolated and characterized the phenotypic, biological, and genomic characteristics of a bacteriophage, vB_PaP_phiPA1-3 (phiPA1-3). Biofilm eradication and phage rescue from bacterial infections were assessed to demonstrate the efficacy of the application potential. Host range spectrum analysis revealed that phiPA1-3 is a moderate host range phage that infects 20% of the clinically isolated strains of P. aeruginosa tested, including carbapenem-resistant P. aeruginosa (CRPA). The phage exhibited stability at pH 7.0 and 9.0, with significantly reduced viability below pH 5.0 and beyond pH 9.0. phiPA1-3 is a lytic phage with a burst size of 619 plaque-forming units/infected cell at 37 °C and can effectively lyse bacteria in a multiplicity of infection-dependent manner. The genome size of phiPA1-3 was found to be 73,402 bp, with a G+C content of 54.7%, containing 93 open reading frames, of which 62 were annotated as hypothetical proteins and the remaining 31 had known functions. The phage possesses several proteins similar to those found in N4-like phages, including three types of RNA polymerases. This study concluded that phiPA1-3 belongs to the N4-like Schitoviridae family, can potentially eradicate P. aeruginosa biofilms, and thus, serve as a valuable tool for controlling CRPA infections.
耐多药铜绿假单胞菌（MDR Pseudomonas aeruginosa）通常导致严重的医院获得性感染。最近，耐碳青霉烯铜绿假单胞菌（Carbapenem-resistant P. aeruginosa）的逐渐出现引起了关注。铜绿假单胞菌介导的多种致病机制，包括其生物膜形成能力，限制了有效抗菌治疗的应用。在本研究中，我们分离并表征了一株噬菌体 vB_PaP_phiPA1-3（phiPA1-3）的表型、生物学和基因组特征。通过评估生物膜清除和噬菌体从细菌感染中的拯救，证明了其应用潜力。宿主范围谱分析表明，phiPA1-3 是一种中等宿主范围的噬菌体，可感染 20%测试的临床分离铜绿假单胞菌菌株，包括耐碳青霉烯铜绿假单胞菌（CRPA）。噬菌体在 pH 值 7.0 和 9.0 下稳定，在 pH 值低于 5.0 和高于 9.0 时活性显著降低。phiPA1-3 是一种裂解噬菌体，在 37°C 时每个感染细胞的爆发量为 619 个噬菌斑形成单位，可以有效地以感染复数依赖性方式裂解细菌。phiPA1-3 的基因组大小为 73,402bp，G+C 含量为 54.7%，包含 93 个开放阅读框，其中 62 个被注释为假设蛋白，其余 31 个具有已知功能。噬菌体具有几种与 N4 样噬菌体相似的蛋白，包括三种 RNA 聚合酶。本研究得出结论，phiPA1-3 属于 N4 样 Schitoviridae 科，能够潜在地清除铜绿假单胞菌生物膜，因此可作为控制 CRPA 感染的有价值工具。
