Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages.

Friends or Foes? Rapid Determination of Dissimilar Colistin and Ciprofloxacin Antagonism of Pseudomonas aeruginosa Phages.
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DOI:
10.3390/ph14111162
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发表时间:
2021-11-15
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
Abedon ST
Abedon ST
中科院分区:
其他
文献类型:
--
作者:
Danis-Wlodarczyk KM;Cai A;Chen A;Gittrich MR;Sullivan MB;Wozniak DJ;Abedon ST

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噬菌体治疗是一种使用病毒(病毒)治疗细菌感染的百年技术,在临床上它经常与抗生素联合使用。然而,抗生素会干扰细菌的关键代谢活动,而这些活动是细菌感染所必需的。然而,噬菌体感染活性的抗生素拮抗作用的明确测试不是噬菌体治疗研究的常见特征。在这里,我们使用光学密度为基础的“裂解配置文件”的测定,以评估两种抗生素,粘菌素和环丙沙星,对三个铜绿假单胞菌的杀菌,溶菌,和新的病毒粒子生产活动的影响。尽管粘菌素和抗生素联合使用比单独使用更有效地杀死铜绿假单胞菌,但粘菌素即使在其最低抑制浓度(1× MIC)下也会显著干扰噬菌体溶菌和病毒体产生活性。相比之下,环丙沙星在1×或3× MIC下几乎没有抗噬菌体作用。我们证实了这些结果与更传统的措施,特别是菌落形成单位,噬菌斑形成单位,和一步生长实验。我们的研究结果表明,环丙沙星可能是有用的,作为一个并行的噬菌体治疗共同治疗,特别是当噬菌体复制是治疗成功所必需的。裂解谱测定也似乎是评估噬菌体感染活性的抗生素拮抗作用的有用、快速和高通量的手段。
Phage therapy is a century-old technique employing viruses (phages) to treat bacterial infections, and in the clinic it is often used in combination with antibiotics. Antibiotics, however, interfere with critical bacterial metabolic activities that can be required by phages. Explicit testing of antibiotic antagonism of phage infection activities, though, is not a common feature of phage therapy studies. Here we use optical density-based ‘lysis-profile’ assays to assess the impact of two antibiotics, colistin and ciprofloxacin, on the bactericidal, bacteriolytic, and new-virion-production activities of three Pseudomonas aeruginosa phages. Though phages and antibiotics in combination are more potent in killing P. aeruginosa than either acting alone, colistin nevertheless substantially interferes with phage bacteriolytic and virion-production activities even at its minimum inhibitory concentration (1× MIC). Ciprofloxacin, by contrast, has little anti-phage impact at 1× or 3× MIC. We corroborate these results with more traditional measures, particularly colony-forming units, plaque-forming units, and one-step growth experiments. Our results suggest that ciprofloxacin could be useful as a concurrent phage therapy co-treatment especially when phage replication is required for treatment success. Lysis-profile assays also appear to be useful, fast, and high-throughput means of assessing antibiotic antagonism of phage infection activities.
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