体宿主范围的扩大通过Klebsiella pneumoniae的高度体耐药菌株的定向进化
Kevin A Burke1, Tracey L Peters2, Olga A Kirillina1
1Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
International journal of molecular sciences
|August 14, 2025
概括
定向进化增强了对抗多药耐药的Klebsiella pneumoniae的细菌体 (菌体) 尾酒. 这种方法产生了具有更广泛宿主范围的菌体变异,显示出对抗耐药细菌感染的前景.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 耐多药性 (MDR) 克莱布西拉肺炎 (Klebsiella pneumoniae) 对全球健康构成重大威胁.
- 菌体疗法是治疗MDR感染的有希望的替代方案,但有限的菌体宿主范围是一个挑战.
研究的目的:
- 通过体外定向进化来增强Klebsiella pneumoniae菌体的宿主范围.
- 开发改进的菌体治疗尾酒,用于对抗MDR K. pneumoniae.
主要方法:
- 利用阿佩尔曼斯的协议进行体外导向进化的五个髓菌体 (Jiaodavirus属).
- 经过混合菌体对抗K. pneumoniae菌株组,包括耐药的临床分离物.
- 对100个菌株的多样性小组测试了进化的菌体变异,以评估宿主范围的变化.
主要成果:
- 隔离的菌体变体具有改变的特异性和扩大的宿主范围.
- 一些变种获得了对先前耐药菌株的活性,而其他变种则显示出更广泛的疗效.
- 全基因组测序揭示了与宿主范围修改相关的尾部纤维基因突变.
结论:
- 定向进化成功地产生了具有更广泛宿主范围的K. pneumoniae菌体.
- 进化菌体是下一代治疗尾酒的有希望的候选人,可以对抗MDR K. pneumoniae.
- 了解遗传变化为菌体与宿主相互作用和治疗发展提供了洞察力.
相关概念视频
00:43Lysogenic Cycle of Bacteriophages
63.2K
In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
63.2K
01:26DNA Bacteriophages
145
Bacteriophages, or phages, are viruses that specifically infect bacteria, utilizing their genetic material to hijack host cellular machinery for replication. DNA bacteriophages employ single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) genomes. These phages exhibit diverse replication strategies and host interactions, influencing their ecological roles and applications in biotechnology and medicine.ssDNA BacteriophagesssDNA phages, with their small genomes, utilize unique strategies to...
145
01:30Lytic Cycle of Bacteriophages
72.0K
Bacteriophages, also known as phages, are specialized viruses that infect bacteria. A key characteristic of phages is their distinctive “head-tail” morphology. A phage begins the infection process (i.e., lytic cycle) by attaching to the outside of a bacterial cell. Attachment is accomplished via proteins in the phage tail that bind to specific receptor proteins on the outer surface of the bacterium. The tail injects the phage’s DNA genome into the bacterial cytoplasm. In the...
72.0K
01:16Viral Replication: Lysogenic Cycle
238
The lysogenic cycle is a crucial viral replication strategy that allows bacteriophages to persist within host cells without immediately destroying them. This process is primarily observed in temperate phages, such as bacteriophage lambda (λ), which infects Escherichia coli. The cycle allows the viral genome to persist across bacterial generations while keeping host cells viable.Integration of the Viral GenomeUpon infection, bacteriophage lambda attaches to the bacterial surface and injects...
238
01:16Transduction
107
Among the three main modes of HGT—transformation, conjugation, and transduction—transduction is unique in that it is mediated by bacteriophages, or bacterial viruses.Transduction occurs in two ways. Generalized transduction occurs during the lytic cycle of a bacteriophage infection. In this process, bacteriophages infect bacterial cells, replicate within them, and ultimately cause cell lysis, releasing newly assembled virions. Occasionally, random fragments of the bacterial genome...
107
01:20Viral Replication: Lytic Cycle
251
Bacteriophages, or phages, are viruses that specifically infect bacteria. Among them, T-even bacteriophages, such as T4, exhibit a well-characterized lytic replication cycle in Escherichia coli (E. coli). This process ensures the rapid proliferation of the virus while ultimately leading to the destruction of the bacterial host.Attachment and DNA InjectionThe infection process begins with the recognition and binding of the T4 phage to the E. coli cell surface. Tail fibers of the phage...
251