Interaction of pneumococcal phase variation, host and pressure/gas composition: Virulence expression of NanA, HylA, PspA and CbpA in simulated otitis media
Interaction of pneumococcal phase variation, host and pressure/gas composition: Virulence expression of NanA, HylA, PspA and CbpA in simulated otitis media
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DOI：
10.1016/j.micpath.2010.05.014
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发表时间：
2010-10-01
影响因子：
3.8
通讯作者：
Banks, Juliane M.
中科院分区：
文献类型：
--
作者：
Li-Korotky, Ha-Sheng;Lo, Chia-Yee;Banks, Juliane M.
肺炎链球菌是中耳炎（OM）的主要病因，其适应宿主环境并在菌落形态上经历自发的菌株内相变化。透明（T）期变异体在鼻咽定殖中更有效，而不透明（O）期变异体在全身感染中表现出更大的毒力。我们最近证明，在与人中耳（ME）相互作用期间，T期变异体比O期变异体表现出更高的生长速率和更大的上皮粘附和破坏。上皮细胞该研究描述了潜在的分子机制将人ME上皮细胞在三种模拟ME气体/压力条件之一下预处理24小时，所述模拟ME气体/压力条件设计用于反映1）正常ME，2）具有咽鼓管阻塞（ETO）的ME和3）具有鼓膜造口管（TT）放置的ME，随后暴露于一定剂量（10（7）CFU/ml）的肺炎链球菌的T或O期变体（6A），然后孵育1小时和3小时，接种物中编码肺炎球菌NanA、HylA、PspA和CbpA毒力因子的基因表达，使用实时PCR分析上皮附着和自由漂浮的细菌。结果显示T接种物中的NanA和HylA的基础表达水平显著高于O接种物。此外，在接种物的形式上观察到两个阶段变体之间的显著差异，T接种物中PspA的表达水平显著更高，但O接种物中CbpA的表达水平显著更高。IT条件增强了上皮附着T阶段变体和流体漂浮O变体中NanA、HylA和PspA毒力因子的分子活性，我们的研究表明，肺炎球菌毒力的时相变化是由病理ME环境和宿主病原体相互作用在OM的发病过程中调制。(C)2010爱思唯尔有限公司版权所有。
Streptococcus pneumoniae, a leading cause of otitis media (OM), adapts to the host environment and undergoes spontaneous intra-strain phase variations in colony morphology. Transparent (T) phase variants are more efficient in colonizing the nasopharynx while the opaque (O) phase variants exhibit greater virulence during systemic infections We recently demonstrated that T phase variants exhibited a higher growth rate and greater epithelial adherence and destruction than did O phase variants during interactions with human middle ear (ME) epithelial cells This study was to delineate the underlying molecular mechanisms Human ME epithelial cells were preconditioned for 24 h under one of the three simulated ME gas/pressure conditions designed to reflect those for 1) normal ME, 2) ME with Eustachian tube obstruction (ETO) and 3) ME with tympanostomy tube (TT) placement, subsequently exposed to a dose (10(7) CFU/ml) of either T or O phase variants of S pneumoniae (6A), and then incubated for 1 h and 3 h Gene expressions coding for pneumococcal NanA, HylA, PspA, and CbpA virulence factors in inoculum, epithelium-attached and free-floating bacteria were assayed using real-time PCR. Result showed significantly higher basal expression levels for NanA and HylA in T inoculums than in O inoculum. Furthermore, striking differences between the two phase variants were observed in the forms of the inocula, significantly higher expression levels for PspA in T inoculum, but for CbpA in O inoculum The IT condition enhanced the molecular activities of NanA, HylA, and PspA virulence factors in epithelium-attached T phase variants and fluid-floating O variants, followed by the ETO condition Our study suggests that the pneumococcal virulence of the phase variations are modulated by the pathological ME environment and host pathogen interaction during the pathogenesis of OM. (C) 2010 Elsevier Ltd. All rights reserved.