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噬菌体-抗生素联合疗法治疗产超广谱β-内酰胺酶肠炎沙门氏菌PT1菌株的评估

Evaluation of phage-antibiotic combinations in the treatment of extended-spectrum β-lactamase-producing enteritidis strain PT1.

作者信息

Alharbi Mona G, Al-Hindi Rashad R, Alotibi Ibrahim A, Azhari Sheren A, Farsi Reem M, Teklemariam Addisu D

机构信息

Department of Biological Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

Health Information Technology Department, Applied College, King Abdulaziz University, Jeddah, 21589, Saudi Arabia.

出版信息

Heliyon. 2023 Jan 19;9(1):e13077. doi: 10.1016/j.heliyon.2023.e13077. eCollection 2023 Jan.

DOI:10.1016/j.heliyon.2023.e13077
PMID:36747932
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9898657/
Abstract

Foodborne infections caused by spp. are among the most common foodborne diseases in the world. We isolated a lytic phage against extended-spectrum beta-lactam producing strain PT1 derived from chicken carcass. Results from electronmicrography indicated that phiPT1 belonged to the family, , in the order, . Phage phiPT1 was stable at temperatures from 4 °C to 60 °C and inactivated at 90 °C. phiPT1 retained a high titer from pH 4 to pH 10 for at least 1 h. Nevertheless, it displayed a significant decrease ( < 0.05) in titer at pH 11 and 12, with phage titers of 5.5 and 2.4 log PFU/mL, respectively. The latent time and burst size of phiPT1 were estimated to be 30 min and 252 PFU/infected cell, respectively. The virulence of phage phiPT1 was evaluated against Enteritidis strain PT1 at different MOIs. phiPT1 reduced proliferation relative to the negative control (MOI 0) at all MOIs ( < 0.05). However, there is no significant difference among the MOIs ( > 0.05). The phage-antibiotic combination analysis (PAS) indicated that synergism was not detected at higher phiPT1 titer (10 PFU/mL) with all tested antibiotics at all subinhibitory concentrations. However, synergistic activities were recorded at 0.25 × MIC of four tested antibiotics: cefixime, gentamicin, ciprofloxacin, and aztreonam in combination with phage at 10, 10 and 10 PFU/mL (ΣFIC ≤0.5). Synergism was detected for all antibiotics (0.1 × MIC) except meropenem and colistin in combination with phiPT1 at 10, 10 and 10 PFU/mL (ΣFIC ≤0.5). Synergism also displayed at the lowest concentrations of all antibiotics (0.01 MIC) in combination with phiPT1 at all titers except 10 PFU/mL. Such characteristic features make phiPT1 to be a potential candidate for therapeutic uses.

摘要

由[具体菌名]引起的食源性感染是世界上最常见的食源性疾病之一。我们从鸡胴体中分离出一株针对产超广谱β-内酰胺酶的[具体菌名]菌株PT1的裂解性噬菌体。电子显微镜观察结果表明,噬菌体phiPT1属于[噬菌体科名]科,[噬菌体目名]目。噬菌体phiPT1在4℃至60℃的温度范围内稳定,在90℃时失活。phiPT1在pH值为4至10时至少1小时内保持高滴度。然而,在pH值为11和12时,其滴度显著下降(P<0.05),噬菌体滴度分别为5.5和2.4 log PFU/mL。phiPT1的潜伏期和裂解量估计分别为30分钟和252 PFU/感染细胞。在不同的感染复数(MOI)下评估了噬菌体phiPT1对肠炎沙门氏菌菌株PT1的毒力。在所有感染复数下,相对于阴性对照(MOI 0),phiPT1均降低了[具体菌名]的增殖(P<0.05)。然而各感染复数之间没有显著差异(P>0.05)。噬菌体-抗生素联合分析(PAS)表明,在所有亚抑菌浓度下,当噬菌体phiPT1滴度较高(10 PFU/mL)时,与所有测试抗生素均未检测到协同作用。然而,在四种测试抗生素(头孢克肟、庆大霉素、环丙沙星和氨曲南)的0.25×最低抑菌浓度(MIC)下,与噬菌体在10、10和10 PFU/mL组合时记录到协同活性(ΣFIC≤0.5)。除美罗培南和黏菌素外,在所有抗生素(0.1×MIC)与phiPT1在10、10和10 PFU/mL组合时(ΣFIC≤0.5)均检测到协同作用。在所有抗生素最低浓度(0.01 MIC)下,与phiPT1在除10 PFU/mL外的所有滴度组合时也显示出协同作用。这些特性使phiPT1成为治疗用途的潜在候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/1248ccc7104d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/d1b5381036a9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/caa70b46709f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/8f03acfe8482/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/ab29b9c39401/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/9613b19311b3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/8cd4de7e17c9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/1248ccc7104d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/d1b5381036a9/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/caa70b46709f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/8f03acfe8482/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/ab29b9c39401/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/9613b19311b3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/8cd4de7e17c9/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b440/9898657/1248ccc7104d/gr7.jpg

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