Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells.
Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells.
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DOI：
10.1111/j.1462-5822.2011.01586.x
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发表时间：
2011-06
影响因子：
3.4
通讯作者：
Edwards JL
中科院分区：
文献类型：
--
作者：
Jennings MP;Jen FE;Roddam LF;Apicella MA;Edwards JL
淋病奈瑟菌表达的Ⅳ型菌毛在介导其对人上皮细胞的黏附过程中起着关键作用。淋球菌菌毛蛋白被一种O - 连接聚糖修饰，由于某些菌毛蛋白糖基化基因的相变，这种聚糖可能以二糖或单糖形式存在。细菌蛋白质可能被糖基化这一观点已被接受；但不太清楚的是蛋白质聚糖如何介导毒力。我们利用原代人宫颈上皮（即pex）细胞，现在提供证据表明菌毛蛋白聚糖介导了有效的宫颈感染。在这方面，菌毛蛋白聚糖缺陷型突变淋球菌表现出早期的高黏附表型，但侵袭pex细胞的能力减弱。我们的数据进一步表明，菌毛蛋白聚糖是淋球菌结合补体受体3的I结构域区域所必需的，而pex细胞天然表达补体受体3。比较性的定量感染试验显示，缺乏菌毛蛋白聚糖的突变淋球菌在补体受体3的I结构域处于闭合的低亲和力构象时不能与之结合，并且在pex细胞攻击过程中不能诱导补体受体3形成活性构象。据我们所知，这些是首次直接证明与蛋白质相关的细菌聚糖如何有助于发病机制的数据。
Expression of type IV pili by Neisseria gonorrhoeae plays a critical role in mediating adherence to human epithelial cells. Gonococcal pilin is modified with an O-linked glycan, which may be present as a di- or monosaccharide because of phase variation of select pilin glycosylation genes. It is accepted that bacterial proteins may be glycosylated; less clear is how the protein glycan may mediate virulence. Using primary, human, cervical epithelial (i.e. pex) cells, we now provide evidence to indicate that the pilin glycan mediates productive cervical infection. In this regard, pilin glycan-deficient mutant gonococci exhibited an early hyper-adhesive phenotype but were attenuated in their ability to invade pex cells. Our data further indicate that the pilin glycan was required for gonococci to bind to the I-domain region of complement receptor 3, which is naturally expressed by pex cells. Comparative, quantitative, infection assays revealed that mutant gonococci lacking the pilin glycan did not bind to the I-domain when it is in a closed, low-affinity conformation and cannot induce an active conformation to complement receptor 3 during pex cell challenge. To our knowledge, these are the first data to directly demonstrate how a protein-associated bacterial glycan may contribute to pathogenesis.
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DOI：
10.1159/000463091
发表时间：
1989-05-01
期刊：
COMPLEMENT AND INFLAMMATION
影响因子：
--
作者：
BECHERER, JD;ALSENZ, J;LAMBRIS, JD
通讯作者：
LAMBRIS, JD
影响因子：
3.1
作者：
Giardina, PC;Williams, R;Apicella, MA
通讯作者：
Apicella, MA
影响因子：
4.8
作者：
Aas, Finn Erik;Egge-Jacobsen, Wolfgang;Koomey, Michael
通讯作者：
Koomey, Michael
影响因子：
3.1
作者：
Edwards, JL;Shao, JQ;Apicella, MA
通讯作者：
Apicella, MA
影响因子：
6.4
作者：
APICELLA, MA
通讯作者：
APICELLA, MA