Miller Isaac P, Laney Alma G, Zahn Geoffrey, Sheehan Brock J, Whitley Kiara V, Kuddus Ruhul H
Department of Biology, Utah Valley University, Orem, UT, United States.
Front Microbiol. 2024 Oct 15;15:1472729. doi: 10.3389/fmicb.2024.1472729. eCollection 2024.
(previously known as K6) strains are among the multidrug-resistant hypervirulent bacterial pathogens. Phage therapy can help treat infections caused by such pathogens. Here we report some aspects of virology and therapeutic potentials of vB_KquU_φKuK6, a bacteriophage that infects
(ATCC 700603) was used to screen wastewater lytic phages. The isolate vB_KquU_φKuK6 that consistently created large clear plaques was characterized using standard virological and molecular methods.
vB_KquU_φKuK6 has a complex capsid with an icosahedral head (60 nm) and a slender tail (140 nm × 10 nm). The phage has a 51% AT-rich linear dsDNA genome (51,251 bp) containing 121 open reading frames. The genome contains genes encoding spanin, endolysin, and holin proteins necessary for lytic infection and a recombinase gene possibly involved in lysogenic infection. vB_KquU_φKuK6 is stable at -80 to +67°C, pH 4-9, and brief exposure to one volume percent of chloroform. vB_KquU_φKuK6 has a narrow host range. Its lytic infection cycle involves a latency of 20 min and a burst size of 435 plaque-forming units. The phage can cause lysogenic infection, and the resulting lysogens are resistant to lytic infection by vB_KquU_φKuK6. vB_KquU_φKuK6 reduces the host cells' ability to form biofilm but fails to eliminate that ability. vB_KquU_φKuK6 demonstrates phage-antibiotic synergy and reduces the minimum inhibitory concentration of chloramphenicol and neomycin sulfate by about 8 folds.
vB_KquU_φKuK6 cannot be directly used for phage therapy because it is a temperate bacteriophage. However, genetically modified strains of vB_KquU_φKuK6 alone or combined with antibiotics or other lytic phages can have therapeutic utilities in treating infections.
(以前称为K6)菌株属于多重耐药性高毒力细菌病原体。噬菌体疗法有助于治疗由此类病原体引起的感染。在此,我们报告了一种感染的噬菌体vB_KquU_φKuK6的病毒学和治疗潜力的一些方面。
使用(美国典型培养物保藏中心700603)筛选废水裂解噬菌体。使用标准病毒学和分子方法对持续产生大的清晰噬菌斑的分离株vB_KquU_φKuK6进行表征。
vB_KquU_φKuK6具有复杂的衣壳,有一个二十面体头部(约60纳米)和一条细长的尾部(约140纳米×10纳米)。该噬菌体有一个富含AT的线性双链DNA基因组(51251碱基对),占51%,包含121个开放阅读框。基因组包含编码裂解感染所需的跨膜蛋白、溶菌酶和穿孔素蛋白的基因,以及一个可能参与溶原性感染的重组酶基因。vB_KquU_φKuK6在-80至+67°C、pH值4-9以及短暂暴露于1%体积的氯仿中时稳定。vB_KquU_φKuK6的宿主范围狭窄。其裂解感染周期包括20分钟的潜伏期和435个噬菌斑形成单位的爆发量。该噬菌体可引起溶原性感染,产生的溶原菌对vB_KquU_φKuK6的裂解感染具有抗性。vB_KquU_φKuK6降低了宿主细胞形成生物膜的能力,但未能消除该能力。vB_KquU_φKuK6表现出噬菌体-抗生素协同作用,并将氯霉素和硫酸新霉素的最低抑菌浓度降低了约8倍。
vB_KquU_φKuK6不能直接用于噬菌体疗法,因为它是一种温和噬菌体。然而,单独的vB_KquU_φKuK6基因改造菌株或与抗生素或其他裂解噬菌体联合使用,在治疗感染方面可能具有治疗效用。