Bacteriophage PEV20 and Ciprofloxacin Combination Treatment Enhances Removal of Pseudomonas aeruginosa Biofilm Isolated from Cystic Fibrosis and Wound Patients
Bacteriophage PEV20 and Ciprofloxacin Combination Treatment Enhances Removal of Pseudomonas aeruginosa Biofilm Isolated from Cystic Fibrosis and Wound Patients
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DOI：
10.1208/s12248-019-0315-0
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发表时间：
2019-05-01
期刊：
影响因子：
4.5
通讯作者：
Chan, Hak-Kim
中科院分区：
文献类型：
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作者：
Chang, Rachel Yoon Kyung;Das, Theerthankar;Chan, Hak-Kim
铜绿假单胞菌生物膜中的抗生素耐药性需要具有抗生物膜性质的新型抗微生物疗法。噬菌体（Bacteriophages，简称BPHs）是一种理想的抗耐药细菌的生物药物，尤其是与抗生素联合使用时。然而，先前的研究主要集中于使用抗实验室菌株的铜绿假单胞菌生物膜的微生物。在本研究中，从囊性纤维化和伤口患者中分离的六株铜绿假单胞菌和一株实验室菌株的生物膜被单独处理，以及用抗假单胞菌噬菌体PEV20和环丙沙星的组合处理。在这些菌株中，三个对噬菌体高度敏感，而一个是部分抗性的，一个是完全抗性的。与单一治疗相比，PEV20和环丙沙星的联合治疗增强了生物膜根除。发现噬菌体和环丙沙星的协同作用取决于靶细菌的噬菌体抗性谱。此外，噬菌体和环丙沙星组合制剂保护肺上皮细胞和成纤维细胞免受铜绿假单胞菌的侵害并促进细胞生长。结果表明，彻底筛选噬菌体抗性是设计噬菌体抗生素制剂的关键。添加高效噬菌体可以降低对抗囊性纤维化和伤口患者中与生物膜相关的铜绿假单胞菌感染所需的环丙沙星浓度。
Antibiotic resistance in Pseudomonas aeruginosa biofilms necessitates the need for novel antimicrobial therapy with anti-biofilm properties. Bacteriophages (phages) are recognized as an ideal biopharmaceutical for combating antibiotic-resistant bacteria especially when used in combination with antibiotics. However, previous studies primarily focused on using phages against of P. aeruginosa biofilms of laboratory strains. In the present study, biofilms of six P. aeruginosa isolated from cystic fibrosis and wound patients, and one laboratory strain was treated singly and with combinations of anti-Pseudomonas phage PEV20 and ciprofloxacin. Of these strains, three were highly susceptible to the phage, while one was partially resistant and one was completely resistant. Combination treatment with PEV20 and ciprofloxacin enhanced biofilm eradication compared with single treatment. Phage and ciprofloxacin synergy was found to depend on phage-resistance profile of the target bacteria. Furthermore, phage and ciprofloxacin combination formulation protected the lung epithelial and fibroblast cells from P. aeruginosa and promoted cell growth. The results demonstrated that thorough screening of phage-resistance is crucial for designing phage-antibiotic formulation. The addition of highly effective phage could reduce the ciprofloxacin concentration required to combat P. aeruginosa infections associated with biofilm in cystic fibrosis and wound patients.