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抗菌肽与传统抗生素联合应用对多重耐药菌的协同作用及抗生物膜活性。

Synergistic effect and antibiofilm activity of an antimicrobial peptide with traditional antibiotics against multi-drug resistant bacteria.

机构信息

Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao, 266003, China.

Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao, 266003, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266003, China.

出版信息

Microb Pathog. 2021 Sep;158:105056. doi: 10.1016/j.micpath.2021.105056. Epub 2021 Jun 18.

Abstract

Combined treatment of AMPs with classical antibiotics has gained interest because it often results in a synergistic antibacterial effect. We demonstrated here that Pt5-1c, an AMP derived from phosvitin, had antibacterial activity against the MDR bacteria (S. aureus USA500, E. coli 577 and K. pneumoniae 2182) in the presence of serum. On this basis, we showed that Pt5-1c was synergistically active with traditional antibiotics (oxacillin, vancomycin, streptomycin and azithromycin) against the three MDR bacteria growing as biofilms in vitro and in vivo. Moreover, Pt5-1c restored sensitivity of S. aureus USA500 to oxacillin and vancomycin, E. coli 577 to streptomycin and K. pneumoniae 2182 to azithromycin. Importantly, long-term exposure to Pt5-1c did not give rise to antimicrobial resistance. Collectively, these data not only suggest a promising combinatorial therapy strategy to combat antibiotics-tolerant infections but also present a possibility of Pt5-1c being used to prolong the application of antibiotics including oxacillin, vancomycin, streptomycin and azithromycin, that are under threat of becoming ineffective due to antibiotic resistance.

摘要

联合应用抗菌肽(AMPs)与经典抗生素已引起关注,因为这通常会产生协同的抗菌作用。我们在此证明,源自卵黄高磷蛋白的 AMP Pt5-1c 在存在血清的情况下对耐多药细菌(金黄色葡萄球菌 USA500、大肠杆菌 577 和肺炎克雷伯菌 2182)具有抗菌活性。在此基础上,我们表明 Pt5-1c 与传统抗生素(苯唑西林、万古霉素、链霉素和阿奇霉素)对三种耐多药细菌在体外和体内形成生物膜时具有协同活性。此外,Pt5-1c 恢复了金黄色葡萄球菌 USA500 对苯唑西林和万古霉素、大肠杆菌 577 对链霉素和肺炎克雷伯菌 2182 对阿奇霉素的敏感性。重要的是,长期暴露于 Pt5-1c 不会导致抗微生物耐药性。总之,这些数据不仅表明了一种有前途的联合治疗策略,可以对抗对抗生素耐受的感染,而且还提出了一种可能性,即可以使用 Pt5-1c 来延长包括苯唑西林、万古霉素、链霉素和阿奇霉素在内的抗生素的应用,这些抗生素由于抗药性而面临失效的威胁。

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