Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis(x) to increase binding to airway epithelial cells.
Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis(x) to increase binding to airway epithelial cells.
复制标题
铜绿假单胞菌pyocyanin用siAllyl-Lewis（X）调节粘蛋白糖基化，以增加与气道上皮细胞的结合。
DOI：
10.1038/mi.2015.119
复制
发表时间：
2016-07
影响因子：
8
通讯作者：
Lau GW
中科院分区：
文献类型：
--
作者：
Jeffries JL;Jia J;Choi W;Choe S;Miao J;Xu Y;Powell R;Lin J;Kuang Z;Gaskins HR;Lau GW
囊性纤维化(CF)患者与呼吸道病原体铜绿假单胞菌(PA)终身肺部感染作斗争。CF呼吸道中粘液过多为PA的生长提供了有利的生态位。与非慢性阻塞性肺疾病患者相比，慢性阻塞性肺疾病患者的呼吸道粘液富含唾液酸氨基-刘易斯-X，这是PA的首选结合受体。值得注意的是，唾液酸路易斯X水平与CF患者的感染严重程度直接相关。然而，PA导致唾液酸化增加的机制尚不清楚。在这项研究中，我们检测了PA毒力因子调节呼吸道粘蛋白唾液酸路易斯X修饰的能力。我们发现绿青素(PCN)在小鼠呼吸道以及原代和永生化的人气道上皮细胞中都是sialyl-leisX的有效诱导剂。PCN通过肿瘤坏死因子-α介导的磷酸肌醇特异性磷脂酶C依赖的途径增加C2/4GnT和ST3Gal-IV的表达，这两种糖基转移酶负责唾液酸路易X的逐步生物合成。此外，PA通过鞭毛帽依赖的方式与预先暴露于PCN的呼吸道上皮细胞更有效地结合。重要的是，抗唾液酸路易X抗体和抗肿瘤坏死因子-α抗体减弱了PA的结合。这些结果表明，PCN通过增加呼吸道粘蛋白与sialyl-leisX的糖基化而分泌PCN，从而为肺的慢性定植创造良好的环境。
Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared to that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewisx, a preferred binding receptor for PA. Notably, the levels of sialyl-Lewisx directly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewisx modification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewisx in both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewisx, through a TNF-α-mediated phosphoinositol-specific phospholipase C (PI-PLC) dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN through a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewisx and anti-TNF-α attenuated PA binding. These results indicate that PCN secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewisx.