Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin
Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin
复制标题
DOI：
10.1515/hsz-2018-0161
复制
发表时间：
2018-10-01
影响因子：
3.7
通讯作者：
Becker, Katrin Anne
中科院分区：
文献类型：
--
作者：
Keitsch, Simone;Riethmueller, Joachim;Becker, Katrin Anne
囊性纤维化（CF）患者肺部感染的金黄色葡萄球菌（S。金黄色葡萄球菌）在疾病的早期发生。导致CF患者感染易感性和介导S.金黄色葡萄球菌的特征很差。因此，我们的目的是确定α毒素的作用，一个主要的S。金黄色葡萄球菌毒素，用于CF小鼠的肺部感染。链球菌感染金黄色葡萄球菌JE 2在CF小鼠中导致严重肺炎，而野生型小鼠几乎不受影响。JE 2-Deltahla α毒素缺陷降低了S.金黄色葡萄球菌。然而，CF小鼠仍然对突变S更敏感。金黄色葡萄球菌菌株比野生型小鼠。色葡萄金黄色葡萄球菌JE 2诱导CF小鼠支气管中神经酰胺的显著增加以及鞘氨醇和酸性神经酰胺酶表达的下调。α-毒素的缺失减少了CF小鼠感染后的这些变化。在野生型小鼠中观察到类似的变化，但水平低得多。我们的数据表明α-毒素的表达是导致S.金黄色葡萄球菌感染的CF小鼠。野生型S.金黄色葡萄球菌诱导神经酰胺的显著增加和鞘氨醇和酸性神经酰胺酶表达的减少，这些变化决定了感染易感性。
Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of alpha-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of alpha-toxin in JE2-Delta hla reduced the pathogenicity of S. aureus in CF mice. However, CF mice were still more susceptible to the mutant S. aureus strain than wildtype mice. The S. aureus JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of alpha-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of a-toxin is a major factor causing S. aureus infections in CF mice. Wildtype S. aureus induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.