分析一种新的噬菌体 KZag1 感染肺炎克雷伯氏菌生物膜的情况：基因组序列和特征。

Analysis of a new phage, KZag1, infecting biofilm of Klebsiella pneumoniae: genome sequence and characterization.

机构信息

Department of Microbiology and Botany, Faculty of Science, Zagazig University, Zagazig, 44519, Egypt.

Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, Giza, Egypt.

出版信息

BMC Microbiol. 2024 Jun 14;24(1):211. doi: 10.1186/s12866-024-03355-9.

DOI:10.1186/s12866-024-03355-9

PMID:38877452

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11179266/

Abstract

BACKGROUND

This study investigates the effectiveness of the bacteriophage KZag1 against drug-resistant Klebsiella pneumoniae, aiming to assess its potential as a therapeutic agent. The novelty lies in the characterization of KZag1, a Myovirus with specific efficacy against multidrug-resistant K. pneumoniae strains. This highlights the significance of exploring alternative strategies, particularly phage therapy, in addressing biofilm-associated infections.

METHODS

KZag1, characterized by a typical Myovirus structure with a 75 ± 5 nm diameter icosahedral head and a 15 ± 5 nm short tail, was evaluated in experimental trials against 15 strains of K. pneumoniae. The infection cycle duration was determined to be 50 min, resulting in an estimated burst size of approximately 83 plaque-forming units per colony-forming unit (PFU/CFU). Stability assessments were conducted within a pH range of 4 to 12 and temperatures ranging from 45°C to 60°C. Biofilm biomass reduction was observed, particularly at a multiplicity of infection (MOI) of 10.

RESULTS

KZag1 demonstrated infection efficacy against 12 out of 15 tested K. pneumoniae strains. The phage exhibited stability across a broad pH range and at elevated temperatures. Notably, treatment with KZag1 significantly reduced K. pneumoniae biofilm biomass, emphasizing its potential in combating biofilm formation. Genomic analysis revealed a complete genome of 157,089 base pairs with a GC content of 46.38%, encompassing 203 open reading frames (ORFs) and a cysteine-specific tRNA sequence. Comparison with phage GP4 highlighted similarities, with KZag1 having a longer genome by approximately 4829 base pairs and a higher GC content by approximately 0.93%. Phylogenetic analysis classified KZag1 within the Myoviridae family.

CONCLUSION

The efficacy of KZag1 against K. pneumoniae biofilm suggests its potential as a therapeutic candidate, especially for drug-resistant infections. Further clinical research is warranted to explore its synergy with other treatments, elucidate genomic traits, compare with Myoviridae phages, and understand its host interactions. These findings underscore the promising role of KZag1 in addressing drug-resistant bacterial infections.

摘要

背景

本研究旨在评估噬菌体 KZag1 对耐多药肺炎克雷伯菌的疗效，以评估其作为治疗剂的潜力。新颖之处在于 KZag1 的特征描述，它是一种具有针对多药耐药肺炎克雷伯菌菌株的特定疗效的肌尾噬菌体。这凸显了探索替代策略的重要性，特别是噬菌体治疗，以解决生物膜相关感染。

方法

KZag1 具有典型的肌尾病毒结构，直径为 75±5nm 的二十面体头部和 15±5nm 的短尾，在针对 15 株肺炎克雷伯菌的实验中进行了评估。感染周期持续时间确定为 50 分钟，导致每个集落形成单位（CFU）的爆发大小约为 83 个噬菌斑形成单位（PFU/CFU）。在 pH 值为 4 到 12 和温度范围从 45°C 到 60°C 的稳定性评估。观察到生物膜生物量减少，特别是在感染复数（MOI）为 10 时。

结果

KZag1 对 15 株测试的肺炎克雷伯菌菌株中的 12 株表现出感染效力。噬菌体在广泛的 pH 范围和高温下表现出稳定性。值得注意的是，用 KZag1 治疗可显著降低肺炎克雷伯菌生物膜生物量，强调其在对抗生物膜形成方面的潜力。基因组分析显示，完整基因组为 157089 个碱基对，GC 含量为 46.38%，包含 203 个开放阅读框（ORFs）和一个半胱氨酸特异性 tRNA 序列。与噬菌体 GP4 的比较突出了相似之处，KZag1 的基因组长约 4829 个碱基对，GC 含量高约 0.93%。系统发育分析将 KZag1 分类为肌尾病毒科。