Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A.
Type IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A.
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IV 型菌毛糖基化介导铜绿假单胞菌对肺表面活性蛋白 A 调理活性的抗性。
DOI：
10.1128/iai.02874-14
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发表时间：
2015
影响因子：
3.1
通讯作者：
Lau,GeeW
中科院分区：
文献类型：
--
作者：
Tan,RommelM;Kuang,Zhizhou;Hao,Yonghua;Lee,Francis;Lee,Timothy;Lee,RyanJ;Lau,GeeW
铜绿假单胞菌是囊性纤维化慢性肺部感染的主要致病菌。以前，我们已经证明，铜绿假单胞菌的IV型菌毛(TFP)介导了对肺表面活性物质蛋白A(SP-A)抗菌作用的抵抗。有趣的是，含有I组菌毛蛋白的铜绿假单胞菌通过TfpO糖基转移酶与单一O-抗原亚基(O-Ag)发生糖基化。重要的是，TfpO介导的O-糖基化对于小鼠肺部的毒力是重要的，例如在表达TfpO的铜绿假单胞菌菌株的CF中更频繁的肺部感染。然而，TFP糖基化在铜绿假单胞菌发病机制中的重要性还不完全清楚。在这里，我们证明了在铜绿假单胞菌临床分离株1244中，通过第一组菌毛蛋白对TFP的糖基化来提高适合度的一种机制。在SP-A+/+与SP-A−/−小鼠的急性肺炎模型上，发现Δ糖基化缺陷突变体在肺部感染中减弱。1244菌株和ΔtfpO菌株对SP-A介导的膜通透性的敏感性相同。相反，ΔtfpO突变体更容易被SP-A和其他肺和循环调理素、SP-D和甘露糖结合凝集素2所调理。重要的是，在没有调理素的情况下，对吞噬细胞增加的敏感性被取消了。这些结果表明，在宿主介导的吞噬过程中，TFP与O-Ag的糖基化特异性地赋予了对调离的抵抗。
Pseudomonas aeruginosa is a major bacterial pathogen commonly associated with chronic lung infections in cystic fibrosis (CF). Previously, we have demonstrated that the type IV pilus (Tfp) of P. aeruginosa mediates resistance to antibacterial effects of pulmonary surfactant protein A (SP-A). Interestingly, P. aeruginosa strains with group I pilins areO-glycosylated through the TfpO glycosyltransferase with a single subunit of O-antigen (O-ag). Importantly, TfpO-mediatedO-glycosylation is important for virulence in mouse lungs, exemplified by more frequent lung infection in CF with TfpO-expressing P. aeruginosa strains. However, the mechanism underlying the importance of Tfp glycosylation in P. aeruginosa pathogenesis is not fully understood. Here, we demonstrated one mechanism of increased fitness mediated byO-glycosylation of group 1 pilins on Tfp in the P. aeruginosa clinical isolate 1244. Using an acute pneumonia model in SP-A+/+versus SP-A−/−mice, theO-glycosylation-deficient ΔtfpOmutant was found to be attenuated in lung infection. Both 1244 and ΔtfpOstrains showed equal levels of susceptibility to SP-A-mediated membrane permeability. In contrast, the ΔtfpOmutant was more susceptible to opsonization by SP-A and by other pulmonary and circulating opsonins, SP-D and mannose binding lectin 2, respectively. Importantly, the increased susceptibility to phagocytosis was abrogated in the absence of opsonins. These results indicate thatO-glycosylation of Tfp with O-ag specifically confers resistance to opsonization during host-mediated phagocytosis.