The periplasmic disulfide oxidoreductase DsbA contributes to Haemophilus influenzae pathogenesis.
The periplasmic disulfide oxidoreductase DsbA contributes to Haemophilus influenzae pathogenesis.
复制标题
周质二硫键氧化还原酶 DsbA 有助于流感嗜血杆菌的发病机制。
DOI：
10.1128/iai.01378-07
复制
发表时间：
2008
影响因子：
3.1
通讯作者：
Akerley,BrianJ
中科院分区：
文献类型：
--
作者：
Rosadini,CharlesV;Wong,SandyMS;Akerley,BrianJ
流感嗜血杆菌是一种专性的人类病原体，持续定植在鼻咽部，当它侵入血液、肺或中耳时引起疾病。在侵袭性疾病期间介导与宿主的关键相互作用的蛋白质可能被分泌。许多分泌蛋白质需要DsbA二硫键氧化还原酶添加二硫键以获得活性或稳定性。在这项研究中，我们评估了H. DsbA的流感发病机制以及DsbA的底物HbpA。突变体H.在动物模型中，具有dsbA的非极性缺失的流感病毒Rd和B型菌株埃根在菌血症方面是减毒的，并且互补菌株表现出与亲本菌株相当的毒力。预测的分泌蛋白在H.流感病毒对其他物种已知的DsbA底物的作用揭示了几种可能有助于dsbA毒力作用的蛋白质。一个候选者，血红素转运蛋白，HbpA，进行了检查，因为外源血红素的有氧生长的H。流感。通过烷基化保护试验证实了HbpA中存在adsbA依赖性二硫键，并且HbpA在adsbA突变体中的丰度较低。hbpA突变体在小鼠模型中表现出减少的菌血症，互补作用使其体内表型恢复到亲本菌株的表型。这些结果表明，dsbA是体内所需的，HbpA和其他DsbA依赖性因子可能参与H。流感发病机制
Haemophilus influenzaeis an obligate human pathogen that persistently colonizes the nasopharynx and causes disease when it invades the bloodstream, lungs, or middle ear. Proteins that mediate critical interactions with the host during invasive disease are likely to be secreted. Many secreted proteins require addition of disulfide bonds by the DsbA disulfide oxidoreductase for activity or stability. In this study, we evaluated the role inH. influenzaepathogenesis of DsbA, as well as HbpA, a substrate of DsbA. Mutants ofH. influenzaeRd and type b strain Eagan having nonpolar deletions ofdsbAwere attenuated for bacteremia in animal models, and complemented strains exhibited virulence equivalent to that of the parental strains. Comparison of predicted secreted proteins inH. influenzaeto known DsbA substrates in other species revealed several proteins that could contribute to the role ofdsbAin virulence. One candidate, the heme transport protein, HbpA, was examined because of the importance of exogenous heme for aerobic growth ofH. influenzae. The presence of adsbA-dependent disulfide bond in HbpA was verified by an alkylation protection assay, and HbpA was less abundant in adsbAmutant. ThehbpAmutant exhibited reduced bacteremia in the mouse model, and complementation restored its in vivo phenotype to that of the parental strain. These results indicate thatdsbAis required in vivo and that HbpA and additional DsbA-dependent factors are likely to participate inH. influenzaepathogenesis.