A role for pneumolysin but not neuraminidase in the hearing loss and cochlear damage induced by experimental pneumococcal meningitis in guinea pigs
A role for pneumolysin but not neuraminidase in the hearing loss and cochlear damage induced by experimental pneumococcal meningitis in guinea pigs
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肺炎球菌溶血素而非神经氨酸酶在豚鼠实验性肺炎球菌脑膜炎引起的听力损失和耳蜗损伤中的作用
DOI：
10.1128/iai.65.11.4411-4418.1997
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发表时间：
1997
影响因子：
3.1
通讯作者：
Timothy J. Mitchell
中科院分区：
文献类型：
--
作者：
Andrew J. Winter;Spiro D. Comis;Michael P. Osborne;M. J. Tarlow;John Stephen;Peter W. Andrew;J. Hill;Timothy J. Mitchell
我们研究了肺炎球菌溶血素和神经氨酸酶在实验性肺炎球菌脑膜炎耳聋和耳蜗损害发病机制中的作用。麻醉豚鼠颅内接种7.5 log 10 CFU的（i）野生型肺炎链球菌D39（n = 8），（ii）PLN-A，一种确定的肺炎链球菌溶血素缺陷型D39的同基因衍生物（n = 5），或（iii）deltaNA 1，一种通过nanA基因的插入重复诱变构建的神经氨酸酶缺陷型D39的新衍生物（n = 5）。为了量化听力损失，每3 h记录一次由音调脉冲诱发的耳蜗圆窗膜听神经复合动作电位，持续12 h。将Corti器官活体内固定，用于随后的高分辨率扫描和透射电子显微镜检查。所有动物的脑膜炎症反应相似。在3至10 kHz的频率范围内，PLN-A诱导的听力损失显著低于D39。接种后12 h 10 kHz时的平均听力损失水平如下：D39，50 dB; deltaNA 1，52 dB（P = 0.76 vs D39），PLN-A，12 dB（P < 0.0001 vs D39）。10 kHz时，D39组的平均听力损失率为4.4 dB/h，deltaNA 1组为4.3 dB/h，PLN-A组仅为1.0 dB/h（与D39组相比P < 0.0001）。化脓性尿道炎具有普遍性。PLN-A在脑脊液中诱导较少蛋白质的积累（P = 0.04相对于D39）。感染D39和deltaNA 1诱导的网状层，感觉毛细胞，支持细胞的Corti器官的显着损害。相比之下，感染PLN-A后，Corti器官几乎完好无损。在脑膜源性耳聋模型中，溶血素似乎是耳蜗损伤的主要原因。神经氨酸酶没有明确的致病作用。
We investigated the roles of pneumolysin and neuraminidase in the pathogenesis of deafness and cochlear damage during experimental pneumococcal meningitis. Anesthetized guinea pigs were inoculated intracranially with 7.5 log10 CFU of either (i) wild-type Streptococcus pneumoniae D39 (n = 8), (ii) PLN-A, a defined isogenic derivative of D39 deficient in pneumolysin (n = 5), or (iii) deltaNA1, a new derivative of D39 deficient in neuraminidase constructed by insertion-duplication mutagenesis of the nanA gene (n = 5). To quantify hearing loss, the auditory nerve compound action potential evoked by a tone pulse was recorded from the round window membrane of the cochlea every 3 h for 12 h. The organ of Corti was intravitally fixed for subsequent examination by high-resolution scanning and transmission electron microscopy. All animals sustained similar meningeal inflammatory responses. PLN-A induced significantly less hearing loss than D39 over the frequency range of 3 to 10 kHz. Levels of mean hearing loss at 10 kHz 12 h postinoculation were as follows: D39, 50 dB; deltaNA1, 52 dB (P = 0.76 versus D39), and PLN-A, 12 dB (P < 0.0001 versus D39). The mean rates of hearing loss at 10 kHz were 4.4 dB/h for D39, 4.3 dB/h for deltaNA1, and just 1.0 dB/h for PLN-A (P < 0.0001 versus D39). Suppurative labyrinthitis was universal. PLN-A induced the accumulation of less protein in the cerebrospinal fluid (P = 0.04 versus D39). Infection with D39 and deltaNA1 induced significant damage to the reticular lamina, the sensory hair cells, and supporting cells of the organ of Corti. By contrast, after infection with PLN-A, the organ of Corti appeared virtually intact. Pneumolysin seems to be the principal cause of cochlear damage in this model of meningogenic deafness. No clear pathogenic role was demonstrated for neuraminidase.
儿童细菌性脑膜炎的耳科特征。
DOI：
10.1016/s0022-3476(85)80664-8
发表时间：
1985
期刊：
The Journal of pediatrics
影响因子：
--
作者：
Eavey,RD;Gao,YZ;Schuknecht,HF;Gonzalez-Pineda,M
通讯作者：
Gonzalez-Pineda,M
肺炎球菌溶血素的细胞毒性和补体活性在肺炎球菌肺炎发病机制中的独特作用。
DOI：
10.1164/ajrccm.153.4.8616564
发表时间：
1996
期刊：
American journal of respiratory and critical care medicine.
影响因子：
--
作者：
Rubins,JB;Charboneau,D;Fasching,C;Berry,AM;Paton,JC;Alexander,JE;Andrew,PW;Mitchell,TJ;Janoff,EN
通讯作者：
Janoff,EN