Moses Sarit, Aftalion Moshe, Mamroud Emanuelle, Rotem Shahar, Steinberger-Levy Ida
Department of Biochemistry and Molecular Genetics, The Israel Institute for Biological Research, Ness-Ziona 74100, Israel.
Microorganisms. 2021 Jun 11;9(6):1278. doi: 10.3390/microorganisms9061278.
Pneumonic plague is a lethal infectious disease caused by , a Tier-1 biothreat agent. Antibiotic treatment can save infected patients; however, therapy should begin within 24 h of symptom onset. As some strains showed an antibiotic resistance phenotype, an antibiotic susceptibility test (AST) must be performed. Performing the Clinical and Laboratory Standards Institute (CLSI)-recommended standard process, which includes bacterial isolation, enumeration and microdilution testing, lasts several days. Thus, rapid AST must be developed. As previously published, the -specific reporter phage ϕA1122:: can serve for rapid identification and AST (ID-AST). Herein, we demonstrate the ability to use ϕA1122:: to determine minimal inhibitory concentration (MIC) values and antibiotic susceptibility categories for various therapeutic antibiotics. We confirmed the assay by testing several nonvirulent isolates with reduced susceptibility to doxycycline or ciprofloxacin. Moreover, the assay can be performed directly on positive human blood cultures. Furthermore, as may naturally or deliberately be spread in the environment, we demonstrate the compatibility of this direct method for this scenario. This direct phage-based ID-AST shortens the time needed for standard AST to less than a day, enabling rapid and correct treatment, which may also prevent the spread of the disease.
肺鼠疫是由一种一级生物威胁病原体引起的致命传染病。抗生素治疗可以挽救感染患者;然而,治疗应在症状出现后24小时内开始。由于一些鼠疫杆菌菌株表现出抗生素耐药表型,必须进行抗生素敏感性试验(AST)。按照临床和实验室标准协会(CLSI)推荐的标准流程进行操作,包括细菌分离、计数和微量稀释试验,需要数天时间。因此,必须开发快速AST。如先前发表的那样,鼠疫杆菌特异性报告噬菌体ϕA1122::可用于快速鉴定和AST(ID-AST)。在此,我们展示了使用ϕA1122::来确定各种鼠疫杆菌治疗性抗生素的最低抑菌浓度(MIC)值和抗生素敏感性类别的能力。我们通过测试几种对多西环素或环丙沙星敏感性降低的无毒鼠疫杆菌分离株来验证该检测方法。此外,该检测方法可直接在阳性人血培养物上进行。此外,由于鼠疫杆菌可能自然或人为地在环境中传播,我们证明了这种直接方法在这种情况下的适用性。这种基于噬菌体的直接ID-AST将标准AST所需的时间缩短至不到一天,能够实现快速且正确的治疗,这也可能防止疾病的传播。