醣分子與感染性疾病

Implicated Roles of Carbohydrates in Infectious Diseases

邱繼輝(Kay-Hooi Khoo)

《化學》 58卷2期 (2000/06) Pp. 295-300

https://doi.org/10.6623/chem.2000031

摘要

直至目前為止，儘管科學家們在生物醫學的研究上有極卓越的進展，感染性疾病仍然對人類的健康造成極大的威脅，尤其是在熱帶及公共衛生體系較落後的開發中國家。真正有預防效能的疫苗種類微乎其微，而具抗藥性之病原菌種類卻急速增加。從病毒、細菌到寄生蟲等各種感染性微生物，已被確認及研究的致病因子不乏其數，並可望隨著其基因體逐一完成定序，更快速有效的被解讀與辨識。此一趨勢下，不能由基因體圖譜直接詮釋的醣類分子，勢必成為決定性的瓶頸。要有效的於新世紀戰勝感染性疾病，便需於醣生物學中取得突破，徹底掌握各病原菌與寄生蟲之醣類分子的結構與其免疫性能。識別自我及非自我是免疫系統的最基本概念。對被侵略者而言，任何在結構上有異於己身的分子皆可能是抗原，足以誘發免疫反應。從演化觀點，微生物的醣分子結構模式是迴異於人類的。許多微生物因而就有效的被辨識與抗禦。反之，能成功感染者則必已演化出對應的策略。一個典型的機制是週期性的變更其表面抗原體，或採取類似金蟬脫殼之計，適期脫落其外膜層，藉此中和宿主的免疫反應。其中，各病菌與寄生蟲都不乏其品種專一性的醣類抗原，或為細胞膜與細胞璧上的多醣體、脂多醣、醣脂肪，或為鍵結在蛋白上的醣鏈，分泌的醣蛋白；因其免疫活性，已廣泛的被用於菌種診斷上。另一常見的策略是模擬宿主，亦即合成額似宿主的醣類結構來修飾表體，使其被宿主誤認為己身而逃過免疫監視系統，並可進一步藉此游刃於宿主本身以醣為基礎的識別系統來完成感染與繁殖。此外，病毒興病原菌常以辨識宿主某一特性的醣質作為其附黏與入侵宿主細胞的有效途徑，許多細菌毒素亦靠醣類受體為附著目標；而我們正可反過來針對此設計藥物，以醣類分子或類似物作為抑制劑，克制傳染病菌或病毒的擴散或其毒素所造成的傷害。

並列摘要

A prerequisite to delineating the immunobiological roles of carbohydrates in infectious diseases is a firm understanding of their structures. Glycan structures as found on a whole range of glycoconjugates from infectious microbes including those on a variety of lipoglycans and glycoproteins, are known to differ substantially from those of their immediate hosts, particularly with respect to the non reducing terminal epitopes. This constitutes the basis of their immunogenicity, based on which the invading microbes are recognized and waded off by the host immune system. On the other hand, the infectious microbes have evolved evasive strategies to avoid recognition and even to exploit the host systems to their advantage. In addition, many of the surface glycans on the host tissues are utilized as specific receptors by a variety of virus, bacteria, and bacterial toxins to achieve effective adhesion, entry, and dissemination. Identification and structural characterization of these virulence factors would pave the way for medical applications in which carbohydrate based drugs, diagnostics, and possibly vaccine can be designed and developed.