Neisseria gonorrhoeaeNGO2105 Is an Autotransporter Protein Involved in Adhesion to Human Cervical Epithelial Cells andin vivoColonization

Neisseria gonorrhoeaeNGO2105 Is an Autotransporter Protein Involved in Adhesion to Human Cervical Epithelial Cells andin vivoColonization
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淋病奈瑟菌 NGO2105 是一种自转运蛋白,参与人宫颈上皮细胞的粘附和体内定植。

DOI:
10.3389/fmicb.2020.01395
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发表时间:
2020-06-25
影响因子:
5.2
通讯作者:
Min, Xun
Min, Xun
中科院分区:
生物学2区
文献类型:
--
作者:
Huang, Jian;Zhang, Qing;Min, Xun

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自身转运蛋白是革兰氏阴性菌外膜上重要的毒力因子。虽然在脑膜炎奈瑟菌中已经鉴定出几种自身转运蛋白,但在淋病奈瑟菌中仅鉴定出IgA 1蛋白酶。序列分析表明,在两个菌株之间的自转运蛋白的分布有显着差异。据推测,只有两个自我转运蛋白,IgA 1蛋白酶和NGO 2105蛋白,可能是由N.淋病在这里,我们描述了NGO 2105,一个新的自身转运蛋白在N。淋病序列比对显示NGO 2105与N中的粘附和穿透蛋白(App)高度相似。脑膜炎我们发现,NGO 2105输出到外膜,切割和释放到培养上清液中的内源性丝氨酸蛋白酶活性在N。淋病和E.杆菌预测的酶催化三联体中的S267 A的定点诱变废除了自身蛋白水解裂解以允许分泌。NGO 2105 β-桶显示出易位异源Hbp过客结构域的能力。NGO 2105参与淋球菌对人宫颈上皮细胞的粘附和侵袭。此外,针对NGO 2105产生的抗体能够阻断淋球菌粘附于人宫颈上皮细胞。Delta ngo 2105突变体和抗Ngo 2105抗血清显著减弱了N.小鼠淋病。总的来说,我们的研究结果表明,新鉴定的丝氨酸蛋白酶自转运蛋白NGO 2105代表一种新的淋球菌毒力因子和潜在的疫苗靶点。
Autotransporters are important virulence factors in the outer membrane of gram-negative bacteria. Although several autotransporters have been identified inNeisseria meningitidis, only IgA1 protease has been identified inNeisseria gonorrhoeae. A sequence analysis showed a marked difference in the distribution of autotransporters between the two strains. It has been speculated that only two autotransporters, the IgA1 protease and the NGO2105 protein, might be encoded byN. gonorrhoeae. Here, we describe the identification of NGO2105, a new autotransporter inN. gonorrhoeae. A sequence alignment showed that NGO2105 is highly similar to the adhesion and penetration protein (App) inN. meningitidis. We found that NGO2105 is exported to the outer membrane, cleaved and released into the culture supernatant by endogenous serine protease activity inN. gonorrhoeaeandE. coli. The site-directed mutagenesis of S267A in the predicted enzyme catalytic triad abolished autoproteolytic cleavage to allow secretion. The NGO2105 beta-barrel shows the ability to translocate the heterologous Hbp passenger domain. NGO2105 is involved in gonococcal adherence to and invasion into human cervical epithelial cells. Furthermore, antibodies raised against NGO2105 are able to block gonococcal adherence to human cervical epithelial cells. The Delta ngo2105mutant and anti-NGO2105 antiserum significantly attenuated the colonization ofN. gonorrhoeaein mice. Collectively, our results suggest that the newly identified serine protease autotransporter NGO2105 represents a novel virulence factor of gonococcus and a potential vaccine target.