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抗菌肽OH-CATH30对耐抗生素铜绿假单胞菌性角膜炎的治疗潜力。

Therapeutic potential of the antimicrobial peptide OH-CATH30 for antibiotic-resistant Pseudomonas aeruginosa keratitis.

作者信息

Li Sheng-An, Liu Jie, Xiang Yang, Wang Yan-Jie, Lee Wen-Hui, Zhang Yun

机构信息

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China Kunming Institute of Zoology, Kunming College of Life Science, University of the Chinese Academy of Science, Beijing, China.

出版信息

Antimicrob Agents Chemother. 2014 Jun;58(6):3144-50. doi: 10.1128/AAC.00095-14. Epub 2014 Mar 17.

Abstract

The therapeutic potential of antimicrobial peptides (AMPs) has been evaluated in many infectious diseases. However, the topical application of AMPs for ocular bacterial infection has not been well investigated. The AMP OH-CATH30, which was identified in the king cobra, exhibits potent antimicrobial activity. In this study, we investigated the therapeutic potential of OH-CATH30 for Pseudomonas aeruginosa keratitis. Ten isolates of P. aeruginosa from individuals with keratitis were susceptible to OH-CATH30 but not to cefoperazone, ciprofloxacin, gentamicin, and levofloxacin. The microdilution checkerboard assay showed that OH-CATH30 exhibited synergistic activity with ciprofloxacin and levofloxacin against antibiotic-resistant P. aeruginosa. Meanwhile, P. aeruginosa did not develop resistance to OH-CATH30, even after exposure at 0.5× the MIC for up to 25 subcultures. Furthermore, treatment with OH-CATH30, alone or in combination with levofloxacin, significantly improved the clinical outcomes of rabbit keratitis induced by antibiotic-resistant P. aeruginosa. Taken together, our data indicate that the topical application of OH-CATH30 is efficacious against drug-resistant P. aeruginosa keratitis. In addition, our study highlights the potential application of AMPs in treating ocular bacterial infections.

摘要

抗菌肽(AMPs)的治疗潜力已在多种传染病中得到评估。然而,AMPs在眼部细菌感染的局部应用尚未得到充分研究。在眼镜王蛇中发现的AMPs OH-CATH30具有强大的抗菌活性。在本研究中,我们研究了OH-CATH30对铜绿假单胞菌性角膜炎的治疗潜力。从角膜炎患者中分离出的10株铜绿假单胞菌对OH-CATH30敏感,但对头孢哌酮、环丙沙星、庆大霉素和左氧氟沙星不敏感。微量稀释棋盘法显示,OH-CATH30与环丙沙星和左氧氟沙星对耐药铜绿假单胞菌具有协同活性。同时,即使在0.5倍最低抑菌浓度下暴露多达25代,铜绿假单胞菌也未对OH-CATH30产生耐药性。此外,单独使用OH-CATH30或与左氧氟沙星联合使用,均可显著改善耐药铜绿假单胞菌诱导的兔角膜炎的临床结局。综上所述,我们的数据表明,局部应用OH-CATH30对耐药铜绿假单胞菌性角膜炎有效。此外,我们的研究突出了AMPs在治疗眼部细菌感染中的潜在应用。

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