近日，來自哈佛醫(yī)學(xué)院的研究者首次發(fā)現(xiàn)致病菌可以破壞機(jī)體粘膜上的保護(hù)性分子,，比如粘蛋白類等,，然后感染機(jī)體的部分組織。研究者的這項(xiàng)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(huì)為診斷,、治療和預(yù)防細(xì)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(xì)菌感染都是通過身體的粘膜來進(jìn)行的，而粘膜恰恰是機(jī)體胃腸道,、呼吸道,、泌尿生殖系統(tǒng)以及眼睛的濕潤(rùn)上皮保護(hù)組織，粘膜的外表面由兩類粘蛋白分子所保護(hù),，一類分泌蛋白和外界異物會(huì)一起被清楚出機(jī)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(gè)物理屏障來阻止?jié)撛诘奈ｋU(xiǎn)物質(zhì)滲透入細(xì)胞膜中,。
粘膜一般會(huì)接觸兩種類型的致病菌,，一種是機(jī)會(huì)致病菌，這類病菌一般會(huì)停留在粘膜的表明,，當(dāng)粘膜上有創(chuàng)傷的時(shí)候,，細(xì)菌便會(huì)順勢(shì)從傷口處進(jìn)入組織進(jìn)行感染，比如金黃色葡萄球菌經(jīng)常會(huì)造成外科等感染,；而另外一種病菌是非機(jī)會(huì)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(shí)驗(yàn)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(jìn)入機(jī)體甚至是在機(jī)體無明顯外傷的時(shí)候,，而且可以快速進(jìn)行擴(kuò)散引起傳染病。
以前關(guān)于流行性感染細(xì)菌通過粘蛋白屏障進(jìn)行感染的相關(guān)研究很少,，研究者猜測(cè)這種流行性細(xì)菌有可能是通過什么途徑將這些保護(hù)屏障-粘蛋白類給移除了,，才會(huì)引起細(xì)菌的感染。為了驗(yàn)證這種假設(shè),，研究者用肺炎鏈球菌進(jìn)行了實(shí)驗(yàn),，這種細(xì)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(xì)胞膜的固定蛋白被破壞掉了,，而且被從細(xì)胞表面釋放掉了，將粘蛋白破壞并釋放掉之后,，細(xì)菌就順其自然的開始進(jìn)入細(xì)胞進(jìn)行感染了,。
運(yùn)用質(zhì)譜法，研究者能夠識(shí)別出一種酶-ZmpC,，當(dāng)把肺炎鏈球菌中編碼該蛋白酶的基因破壞掉之后,，細(xì)菌就不能破壞并且移除細(xì)胞膜表面的粘蛋白了，研究者Gipson表示,，他們這項(xiàng)研究揭示了流行性細(xì)菌為什么可以輕松進(jìn)入機(jī)體并且引起感染,，而且對(duì)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.
