人類抗菌胜肽LL-37對鮑氏不動桿菌作用機制之研究

Studying the mode of action of human antimicrobial peptide LL-37 on Acinetobacter baumannii

陳正益

指導教授 ： 藍忠昱

國立清華大學/生命科學院/分子與細胞生物研究所/碩士(2013年)

https://doi.org/10.6843/NTHU.2013.00009

摘要

鮑氏不動桿菌是一種格蘭氏陰性的球桿菌，且為人類伺機感染病菌。在正常人體中共生存在，但在免疫能力低下的病人容易起而致病，嚴重則可能導致死亡。近年來全球出現許多不同的多重抗藥性鮑氏不動桿菌菌株，在臨床治療上造成了很大的困難。例如對抗鮑氏不動桿菌最後一道防線之藥物Tigecycline及Colistin，目前也已經有抗藥性菌株的出現，因此必需儘速尋找或研發新抗生素或其他有效抗菌物質，以克服鮑氏不動桿菌的感染問題。本研究中，我們發現人類抗菌胜肽LL-37能夠有效殺害鮑氏不動桿菌，並且在非致死劑量之下能抑制細菌貼附及移動能力。由鮑氏不動桿菌細胞萃取的脂多醣體(Lipopolysaccharide)能夠有效和LL-37競爭，使得細菌貼附能力得以恢復。除此之外、脂多醣體缺失的鮑氏不動桿菌變異株對LL-37有較高的抗性，推測LL-37有可能透過與脂多醣體之接合反應而造成細菌貼附能力之下降。除了脂多醣體，我們也發現LL-37會結合到鮑氏不動桿菌的外膜蛋白A (OmpA)。雖然外膜蛋白A和細菌貼附能力有很大相關，但和LL-37造成的貼附能力下降可能沒有直接的關聯。在實驗中也發現脂多醣體和外膜蛋白A的缺陷都會導致菌体對LL-37的敏感性。綜合上述結果，LL-37可能是一個具有潛力且未來能夠用於治療鮑氏不動桿菌感染的新試劑。

關鍵字

鮑氏不動桿菌 ； LL-37

並列摘要

Acinetobacter baumannii is a Gram-negative coccobacillus and is a leading nosocomial pathogen worldwide. Recently, emergence of multidrug resistant A. baumannii has become a great threat to healthcare. Strains resist to the last line of anti-mocrobial agents, tigecycline and colistin, were appeared. Therefore, developing new drugs to treat A. baumannii infections is urgently needed. In this work, a human antimicrobial peptide LL-37 was evaluated for its effects on A. baumannii. We found that LL-37 kills A. baumannii efficiently and reduces cell adhesion and motility. Lipopolysaccharides extracted from A. baumannii cell surface can rescue LL37-mediated inhibition of cell adhesion. Moreover, far-western analysis indicated that LL-37 binds to outer membrane OmpA protein of A. baumannii (AbOmpA), but this binding seems not to correlate with the inhibitory effect on cell adhesion. However, both LPS and AbOmpA were related to sensitivity of A. baumannii to LL-37. Together, this study suggested that LL-37 may be a potential agent in the future treatment of A. baumannii infections.

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