在試管內及動物模式中鑑定能夠對抗耐甲氧西林金黃葡萄球菌和多重抗藥鮑曼不動桿菌的抗菌胜肽

由於近年來抗生素的大量廣泛使用，抗藥細菌已經出現並且已經成為一個全球的健康議題。因此，目前迫切需要開發具有不同作用機制的新型抗菌藥物。最近，在生物體中發現的一些抗菌胜肽（antimicrobial peptides, AMPs）被發現會透過過破壞膜完整性或者影響細胞內重要的合成途徑，例如DNA或蛋白質的合成，進而殺死細菌。在這個研究中，我們將鑑定能有效對抗並抑制抗藥細菌的AMP，包含抗甲氧西林金黃葡萄球菌（Methicillin resistant Staphylococcus aureus, MRSA）和多重抗藥鮑曼氏不動桿菌（Multi-drug resistant Acinetobacter baumannii, MDRAB）。在已測試的AMP中，SMAP-29對許多包括MRSA和MDRAB的細菌具有廣效性的抑菌能力。其他AMP如Nigrocin和OdP1a對金黃葡萄球菌生物膜形成具有抑制能力。另外我們發現，幾乎所有的AMP都對MDRAB具有較高的抑菌能力，而MDRAB是目前在院內感染中的相當棘手的問題。這些抗菌肽不僅可以抑制細菌生長，而且可以減少生物膜形成。我們也建立了一個小鼠肺炎模型來進一步評估這些AMP在體內的效用，期望具有體內功效的AMP能夠在將來具有臨床應用的潛力。

關鍵字

抗菌胜肽；生物膜；抗甲氧西林金黃葡萄球菌；多重抗藥鮑曼氏不動桿菌；小鼠肺炎模型

並列摘要

Antibiotics-resistant bacteria have emerged due to the widespread usage of antibiotics. Thus, development of new antimicrobial agents with different action mechanisms is acute and urgent. Recently, some antimicrobial peptides (AMPs) found in organisms have shown to have bactericidal abilities by disrupting the membrane integrity or by inhibiting important pathways inside the cell such as DNA replication and protein synthesis. In this project, we will identify the AMPs exhibiting efficient antimicrobial activity against antibiotic-resistant bacteria, including methicillin- resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDRAB). Among the tested AMPs, SMAP-29 and TP4 have a broad-spectrum bactericidal effect toward many kinds of bacteria, including MRSA and MDRAB. Other AMPs such as Nigrocin and OdP1a, have inhibitory effect on S. aureus biofilm formation. Interestingly, all the AMPs exhibit antimicrobial activities against MDRAB, which is a refractory issue in intensive care unit or nosocomial infection. These AMPs can not only inhibit the bacteria growth but also decrease the biofilm formation. We also established a mouse pneumonia model to evaluate the effect of these tested AMPs. The AMPs, which have the in vivo efficacy, will be anticipated to have the potential for the clinical application in the future.

並列關鍵字

AMPs ； biofilms ； MRSA ； MDRAB ； mouse pneumonia model

參考文獻

1. Baron S, 1928-, Medicine. NLo: Medical Microbiology, 4 edn. Galveston, Texas: University of Texas Medical Branch at Galveston; 1996.

2. Schenck LP, Surette MG, Bowdish DM: Composition and immunological significance of the upper respiratory tract microbiota. FEBS Lett 2016, 590(21):3705-3720.

3. Tong SY, Davis JS, Eichenberger E, Holland TL, Fowler VG, Jr.: Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015, 28(3):603-661.

4. Argudin MA, Mendoza MC, Rodicio MR: Food poisoning and Staphylococcus aureus enterotoxins. Toxins (Basel) 2010, 2(7):1751-1773.

5. Ragle BE, Karginov VA, Bubeck Wardenburg J: Prevention and treatment of Staphylococcus aureus pneumonia with a beta-cyclodextrin derivative. Antimicrob Agents Chemother 2010, 54(1):298-304.

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在試管內及動物模式中鑑定能夠對抗耐甲氧西林金黃葡萄球菌和多重抗藥鮑曼不動桿菌的抗菌胜肽

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