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一种新型噬菌体作为靶向多重耐药肺炎克雷伯菌的有前景生物制剂的分析

Analysis of a novel phage as a promising biological agent targeting multidrug resistant Klebsiella pneumoniae.

作者信息

Abdel-Razek Mahmoud A, Nazeih Shaimaa I, Yousef Nehal, Askoura Momen

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 45519, Egypt.

出版信息

AMB Express. 2025 Mar 5;15(1):37. doi: 10.1186/s13568-025-01846-0.

Abstract

The rise of deaths by resistant bacteria is a global threat to public health systems. Klebsiella pneumoniae is a virulent pathogen that causes serious nosocomial infections. The major obstacle to bacterial treatment is antibiotic resistance, which necessitates the introducing of alternative therapies. Phage therapy has been regarded as a promising avenue to fight multidrug-resistant (MDR) pathogens. In the current study, a novel phage vB_KpnP_KP17 was isolated from sewage, and its lytic potential was investigated against K. pneumoniae. The isolated phage vB_KpnP_kP17 was lytic to 17.5% of tested K. pneumoniae isolates. One step growth curve indicated a virulent phage with a short latent period (20 min) and large burst size (331 PFU/cell). Additionally, vB_KpnP_kP17 maintained its activity against planktonic cells over a wide range of pH, temperature and UV irradiation intervals. The potential of vB_KpnP_KP17 as antibiofilm agent was revealed by the biofilm inhibition assay. The isolated phage vB_KpnP_KP17 at multiplicity of infection (MOI) of 10 inhibited more than 50% of attached biofilms of tested K. pneumoniae isolates. The genome of vB_KpnP_kP17 was characterized and found to be a linear dsDNA of 39,936 bp in length and GC content of 52.85%. Additionally, the absence of toxicity, virulence and antibiotic resistance genes further confirms the safety of vB_KpnP_KP17 for clinical applications. These characteristics make vB_KpnP_KP17 of a potential therapeutic value to manage MDR K. pneumoniae infections. Additionally, the formulation of vB_KpnP_KP17 in a cocktail with other lytic phages or with antibiotics could be applied to further limit biofilm-producing K. pneumoniae infections.

摘要

耐药细菌导致的死亡人数上升对公共卫生系统构成了全球性威胁。肺炎克雷伯菌是一种致病性很强的病原体,可引发严重的医院感染。细菌治疗的主要障碍是抗生素耐药性,这就需要引入替代疗法。噬菌体疗法被视为对抗多重耐药(MDR)病原体的一条有前景的途径。在本研究中,从污水中分离出一种新型噬菌体vB_KpnP_KP17,并研究了其对肺炎克雷伯菌的裂解潜力。分离出的噬菌体vB_KpnP_kP17对17.5%的受试肺炎克雷伯菌分离株具有裂解作用。一步生长曲线表明该噬菌体是一种烈性噬菌体,潜伏期短(20分钟),裂解量高(331个噬菌斑形成单位/细胞)。此外,vB_KpnP_kP17在很宽的pH值、温度和紫外线照射时间范围内都能保持对浮游细胞的活性。生物膜抑制试验揭示了vB_KpnP_KP17作为抗生物膜剂的潜力。感染复数(MOI)为10时,分离出的噬菌体vB_KpnP_KP17可抑制受试肺炎克雷伯菌分离株超过50%的附着生物膜。对vB_KpnP_kP17的基因组进行了表征,发现其为线性双链DNA,长度为39,936 bp,GC含量为52.85%。此外,该噬菌体不存在毒性、毒力和抗生素耐药基因,这进一步证实了vB_KpnP_KP17用于临床的安全性。这些特性使vB_KpnP_KP17在治疗多重耐药肺炎克雷伯菌感染方面具有潜在的治疗价值。此外,将vB_KpnP_KP17与其他裂解性噬菌体或抗生素配制成鸡尾酒制剂,可用于进一步限制产生物膜的肺炎克雷伯菌感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54ff/11882492/be4981942093/13568_2025_1846_Fig1_HTML.jpg

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