Staphylococcus aureus Impacts Pseudomonas aeruginosa Chronic Respiratory Disease in Murine Models
Staphylococcus aureus Impacts Pseudomonas aeruginosa Chronic Respiratory Disease in Murine Models
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DOI：
10.1093/infdis/jix621
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发表时间：
2018-03-15
影响因子：
6.4
通讯作者：
Bragonzi, Alessandra
中科院分区：
文献类型：
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作者：
Cigana, Cristina;Bianconi, Irene;Bragonzi, Alessandra
已经建立了慢性感染的小鼠模型，以跟踪CF患者肺部疾病的发生顺序。这些模型揭示了S金黄色葡萄球菌感染在肺部发病机制中的作用及对早期铜绿假单胞菌感染的影响。金黄色葡萄球菌和铜绿假单胞菌是囊性纤维化患者呼吸道的主要病原菌。虽然铜绿假单胞菌慢性支气管感染与较差的预后相关，但金黄色葡萄球菌定植对慢性支气管炎预后的影响是有争议的。在本文中，使用模拟慢性支气管炎患者肺部疾病发生顺序的感染程序，重新建立了类似于慢性支气管炎人类呼吸道疾病特征的小鼠感染模型。首先，小鼠感染包埋在琼脂微珠中的金黄色葡萄球菌；然后是铜绿假单胞菌感染，并对细菌负荷、白细胞渗透和肺组织损伤进行分析。我们发现(1)金黄色葡萄球菌促进包括脓肿形成在内的严重损害，(2)金黄色葡萄球菌增加随后慢性铜绿假单胞菌呼吸道感染的风险，(3)一旦慢性感染已经建立，铜绿假单胞菌影响大多数炎症反应，而不是金黄色葡萄球菌。我们的研究结果确立了金黄色葡萄球菌定植本身的意义及其对后续铜绿假单胞菌感染的影响。这将指向对治疗金黄色葡萄球菌的需要进行彻底评估。
Murine models of chronic infection have been established to follow sequence of events of pulmonary disease in CF patients. These models revealed that S aureus infection contributes to lung pathogenesis and has an impact on early P aeruginosa infection.Staphylococcus aureus and Pseudomonas aeruginosa are key bacterial pathogens of the respiratory tract in patients with cystic fibrosis (CF). Although P. aeruginosa chronic bronchial infection is associated with a poorer prognosis, the consequences of S. aureus colonization on CF outcomes are controversial.In this paper, murine models of infection resembling traits of the CF human airways disease have been revisited using an infection schedule that mimics the sequence of events of pulmonary disease in CF patients. First, mice were infected with S. aureus, embedded in agar beads; this was followed by P. aeruginosa infection and analysis of bacterial load, leukocyte infiltration, and lung tissue damage.We reveal that (1) S. aureus promotes severe lesions including abscess formation, (2) S. aureus increases the risk of subsequent chronic P. aeruginosa respiratory infection, and (3) once the chronic infection has been established, P. aeruginosa influences most of the inflammatory responses independent of S. aureus.Our findings established the significance of S. aureus colonization per se and the impact on the subsequent P. aeruginosa infection. This would point towards a thorough assessment for the need of treatment against S. aureus.