近日,，來自哈佛醫(yī)學院的研究者首次發(fā)現(xiàn)致病菌可以破壞機體粘膜上的保護性分子，比如粘蛋白類等,，然后感染機體的部分組織,。研究者的這項最新研究刊登在了雜志PLoS One上，文章中,，研究者揭示了流行性菌株肺炎鏈球菌可以引起結(jié)膜炎,，并且分泌毒素酶類來破壞粘膜蛋白以及粘膜從而引起眼鏡的感染和發(fā)炎,。
研究者表示他們的研究將會為診斷、治療和預(yù)防細菌感染提供新的方法,，不僅僅是在眼睛的感染上,，而且適用于身體其它部分的感染的治療。超過80%的細菌感染都是通過身體的粘膜來進行的,，而粘膜恰恰是機體胃腸道,、呼吸道、泌尿生殖系統(tǒng)以及眼睛的濕潤上皮保護組織,，粘膜的外表面由兩類粘蛋白分子所保護,，一類分泌蛋白和外界異物會一起被清楚出機體，而另一類繼續(xù)粘附在外表面,。后者的粘蛋白分子組成了一個物理屏障來阻止?jié)撛诘奈ｋU物質(zhì)滲透入細胞膜中,。
粘膜一般會接觸兩種類型的致病菌，一種是機會致病菌,，這類病菌一般會停留在粘膜的表明,，當粘膜上有創(chuàng)傷的時候，細菌便會順勢從傷口處進入組織進行感染,，比如金黃色葡萄球菌經(jīng)常會造成外科等感染,；而另外一種病菌是非機會性的或者說是流行性的，這種病菌可以引起更加侵入性和攻擊性的感染,，比如說在本實驗中所用到的肺炎鏈球菌所引起的流行性結(jié)膜炎,，這些病菌可以直接進入機體甚至是在機體無明顯外傷的時候，而且可以快速進行擴散引起傳染病,。
以前關(guān)于流行性感染細菌通過粘蛋白屏障進行感染的相關(guān)研究很少,，研究者猜測這種流行性細菌有可能是通過什么途徑將這些保護屏障-粘蛋白類給移除了，才會引起細菌的感染,。為了驗證這種假設(shè),，研究者用肺炎鏈球菌進行了實驗，這種細菌可以引起結(jié)膜炎,、眼瞼炎癥等感染,，研究者模擬了眼睛表面的環(huán)境，包括完整的粘蛋白,，研究者發(fā)現(xiàn),，在這種模擬環(huán)境中，受感染的眼鏡表面細胞膜的固定蛋白被破壞掉了,，而且被從細胞表面釋放掉了,，將粘蛋白破壞并釋放掉之后，細菌就順其自然的開始進入細胞進行感染了,。
運用質(zhì)譜法,，研究者能夠識別出一種酶-ZmpC,，當把肺炎鏈球菌中編碼該蛋白酶的基因破壞掉之后，細菌就不能破壞并且移除細胞膜表面的粘蛋白了,，研究者Gipson表示,，他們這項研究揭示了流行性細菌為什么可以輕松進入機體并且引起感染，而且對于臨床上用藥也提供了一些幫助,。（生物谷T.Shen編譯）
doi:10.1371/journal.pone.0032418
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A Metalloproteinase Secreted by Streptococcus pneumoniae Removes Membrane Mucin MUC16 from the Epithelial Glycocalyx Barrier
Bharathi Govindarajan#, Balaraj B. Menon#, Sandra Spurr-Michaud, Komal Rastogi, Michael S. Gilmore, Pablo Argüeso, Ilene K. Gipson*
The majority of bacterial infections occur across wet-surfaced mucosal epithelia, including those that cover the eye, respiratory tract, gastrointestinal tract and genitourinary tract. The apical surface of all these mucosal epithelia is covered by a heavily glycosylated glycocalyx, a major component of which are membrane-associated mucins (MAMs). MAMs form a barrier that serves as one of the first lines of defense against invading bacteria. While opportunistic bacteria rely on pre-existing defects or wounds to gain entry to epithelia, non opportunistic bacteria, especially the epidemic disease-causing ones, gain access to epithelial cells without evidence of predisposing injury. The molecular mechanisms employed by these non opportunistic pathogens to breach the MAM barrier remain unknown. To test the hypothesis that disease-causing non opportunistic bacteria gain access to the epithelium by removal of MAMs, corneal, conjunctival, and tracheobronchial epithelial cells, cultured to differentiate to express the MAMs, MUCs 1, 4, and 16, were exposed to a non encapsulated, non typeable strain of Streptococcus pneumoniae (SP168), which causes epidemic conjunctivitis. The ability of strain SP168 to induce MAM ectodomain release from epithelia was compared to that of other strains of S. pneumoniae, as well as the opportunistic pathogen Staphylococcus aureus. The experiments reported herein demonstrate that the epidemic disease-causing S. pneumoniae species secretes a metalloproteinase, ZmpC, which selectively induces ectodomain shedding of the MAM MUC16. Furthermore, ZmpC-induced removal of MUC16 from the epithelium leads to loss of the glycocalyx barrier function and enhanced internalization of the bacterium. These data suggest that removal of MAMs by bacterial enzymes may be an important virulence mechanism employed by disease-causing non opportunistic bacteria to gain access to epithelial cells to cause infection.
