近日，来自哈佛医学院的研究者首次发现致病菌可以破坏机体粘膜上的保护性分子，比如粘蛋白类等，然后感染机体的部分组织。研究者的这项最新研究刊登在了杂志PLoS One上，文章中，研究者揭示了流行性菌株肺炎链球菌可以引起结膜炎，并且分泌毒素酶类来破坏粘膜蛋白以及粘膜从而引起眼镜的感染和发炎。
研究者表示他们的研究将会为诊断、治疗和预防细菌感染提供新的方法，不仅仅是在眼睛的感染上，而且适用于身体其它部分的感染的治疗。超过80%的细菌感染都是通过身体的粘膜来进行的，而粘膜恰恰是机体胃肠道、呼吸道、泌尿生殖系统以及眼睛的湿润上皮保护组织，粘膜的外表面由两类粘蛋白分子所保护，一类分泌蛋白和外界异物会一起被清楚出机体，而另一类继续粘附在外表面。后者的粘蛋白分子组成了一个物理屏障来阻止潜在的危险物质渗透入细胞膜中。
粘膜一般会接触两种类型的致病菌，一种是机会致病菌，这类病菌一般会停留在粘膜的表明，当粘膜上有创伤的时候，细菌便会顺势从伤口处进入组织进行感染，比如金黄色葡萄球菌经常会造成外科等感染；而另外一种病菌是非机会性的或者说是流行性的，这种病菌可以引起更加侵入性和攻击性的感染，比如说在本实验中所用到的肺炎链球菌所引起的流行性结膜炎，这些病菌可以直接进入机体甚至是在机体无明显外伤的时候，而且可以快速进行扩散引起传染病。
以前关于流行性感染细菌通过粘蛋白屏障进行感染的相关研究很少，研究者猜测这种流行性细菌有可能是通过什么途径将这些保护屏障-粘蛋白类给移除了，才会引起细菌的感染。为了验证这种假设，研究者用肺炎链球菌进行了实验，这种细菌可以引起结膜炎、眼睑炎症等感染，研究者模拟了眼睛表面的环境，包括完整的粘蛋白，研究者发现，在这种模拟环境中，受感染的眼镜表面细胞膜的固定蛋白被破坏掉了，而且被从细胞表面释放掉了，将粘蛋白破坏并释放掉之后，细菌就顺其自然的开始进入细胞进行感染了。
运用质谱法，研究者能够识别出一种酶-ZmpC，当把肺炎链球菌中编码该蛋白酶的基因破坏掉之后，细菌就不能破坏并且移除细胞膜表面的粘蛋白了，研究者Gipson表示，他们这项研究揭示了流行性细菌为什么可以轻松进入机体并且引起感染，而且对于临床上用药也提供了一些帮助。（生物谷T.Shen编译）
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.
