臨床鮑氏不動桿菌SK44莢膜多醣結構鑑定及免疫特性之探討

鮑氏不動桿菌(Acinetobacter baumannii)是一種廣泛分佈於醫院環境的格蘭氏陰性細菌，容易感染一些免疫力差或是手術後的病人。雖然一般鮑氏不動桿菌被認定為低致病力的細菌，但是其所具有的多重抗藥性或是全抗藥性，促使其有能力存活並且誘發嚴重的感染或敗血症等。在預防病菌感染上，細菌的多醣共軛疫苗一些有成功的實例，例如在肺炎鏈球菌(Streptococcus pneumonia)和腦膜炎雙球菌(Neisseria meningitides)的預防上，都有不錯的成效。在此論文中，我們利用噬菌體ΦAB2的尾巴蛋白，其具有將臨床鮑氏不動桿菌的莢膜多醣水解成寡醣或是較小醣鏈片段，並經由氣相層析質譜儀(GC-MS)和核磁共振(NMR)分析其組成及鍵結得知其莢膜多糖是由Glucose、Galactose、N-acetyl-glucosamine (GlcNAc) 和N-acetyl-galactosamine (GalNAc)所組成，而Glucose 和 Galactose則具有1，4和1，4，6兩種形式的醣鍵結。在進一步質譜(MS/MS)分析後，發現寡醣的重複單元很有可能是由4個六碳醣(hexose)和2個帶乙醯基的氨基六碳醣(hexamine)所組成。在免疫特性測試上，巨噬細胞(macrophage)在莢膜多醣刺激後，可誘發一氧化氮(nitric oxide) 、介白素-6(interleukin-6)和腫瘤壞死因子α(TNF-α)產生；大白兔在脾臟注射莢膜多醣後，也成功誘導高效價和高專一抗體產生。雖然就目前的了解,，僅能推測莢膜多糖可能的結構，但希望這些訊息有助於鮑氏不動桿菌(Acinetobacter baumannii)的莢膜研究以及醣疫苗的開發。

關鍵字

鮑氏不動桿菌；莢膜多醣；一氧化氮；介白素-6 ；腫瘤壞死因子α ；氣相層析質譜儀；核磁共振；醣共軛疫苗；組成；鍵結

並列摘要

Abstract Acinetobacter baumannii, causes the serious nosocomial infection in immunocompromised patients or those who have been undergone surgery. The emergence of its multi-drug or even pandrug resistant isolates has made it to eradicate, turning it into a critical medical issue. Glycoconjugate vaccines offer one kind of solution to this bacterial infection. Structural information of the capsular polysaccharide is important for vaccine development. Therefore, in this study, we used a tail fiber protein isolated from bacteriophage ΦAB2 to cleave the capsular polysaccharide (CPS) of Acinetobacter baumannii clinical strain SK44 into smaller sugar fragments. After sugar composition and linkage analysis by gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR), the capsular polysaccharide of SK44 was found to be composed of glucose, galactose, N-acetyl-glucoasamine (GlcNAc) and N-acetyl-galactosamine (GalNAc). The sugar linkages for hexoses contained both 1,6 and 1,4,6 types. In addition, the MS/MS spectra showed that the CPS of SK44 might be a 6 sugars repeat unit (including 4 hexoses and 2 hexamines). In terms of immune properties, the SK44 CPS was found to stimulate nitric oxide, IL-6 and TNF-α production in macrophages. High titer antibodies were also induced after SK44 CPS was injected into the rabbit spleen. We hope these data are useful for the further study.

並列關鍵字

Acinetobacter baumannii ； capsular polysaccharide ； nitric oxide ； interleukin-6 ； TNF-α ； GC-MS ； NMR ； glycoconjuagte vaccine ； sugar composition ； sugar linkage

參考文獻

1 Seifert, H. et al. Distribution of Acinetobacter species on human skin: comparison of phenotypic and genotypic identification methods. J Clin Microbiol 35, 2819-2825 (1997).

2 Yavankar, S. P., Pardesi, K. R. & Chopade, B. A. Species distribution and physiological characterization of Acinetobacter genospecies from healthy human skin of tribal population in India. Indian J Med Microbiol 25, 336-345 (2007).

3 Webster, C., Towner, K. J. & Humphreys, H. Survival of Acinetobacter on three clinically related inanimate surfaces. Infect Control Hosp Epidemiol 21, 246, doi:10.1086/503214 (2000).

4 Larson, E. L. Persistent carriage of gram-negative bacteria on hands. Am J Infect Control 9, 112-119 (1981).

5 Wendt, C., Dietze, B., Dietz, E. & Ruden, H. Survival of Acinetobacter baumannii on dry surfaces. J Clin Microbiol 35, 1394-1397 (1997).

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臨床鮑氏不動桿菌SK44莢膜多醣結構鑑定及免疫特性之探討

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