Mongodin Emmanuel, Bajolet Odile, Cutrona Jérôme, Bonnet Noël, Dupuit Florence, Puchelle Edith, de Bentzmann Sophie
INSERM UMRS514, IFR53, CHU Maison-Blanche. Laboratoire de Bactériologie-Virologie-Hygiène, CHU Robert Debré, 51092 Reims Cedex, France.
Infect Immun. 2002 Feb;70(2):620-30. doi: 10.1128/IAI.70.2.620-630.2002.
This study was designed to investigate the molecular mechanisms of Staphylococcus aureus adherence to human airway epithelium. Using a humanized bronchial xenograft model in the nude mouse and primary cultures of human airway epithelial cells (HAEC), we showed that S. aureus adhered mainly to undifferentiated HAEC whereas weak adherence (11- to 20-fold lower) to differentiated HAEC was observed (P < 0.01). A fibronectin (FN)-binding protein (FnBP)-deficient strain of S. aureus had a fivefold-lower adherence level to undifferentiated HAEC than did the parental strain (P < 0.005), suggesting that S. aureus FN-binding capacity is involved in the adherence to HAEC. We also showed that 97% of 32 S. aureus clinical strains, isolated from the airway secretions of cystic fibrosis patients (n = 18) and patients with nosocomial pneumonia (n = 14), possessed the two fnb genes. The strains from pneumonia patients had a significantly (P < 0.05) higher FN-binding capacity than did the strains from CF patients. This result was confirmed by the expression of FnBPs, investigated by Western ligand affinity blotting. Our results suggest a major role of FnBPs in the colonization of the airways by S. aureus and point to the importance of the adhesin regulatory pathways in the staphylococcal infectious process.
本研究旨在探讨金黄色葡萄球菌黏附于人呼吸道上皮细胞的分子机制。利用裸鼠体内的人源化支气管异种移植模型和人呼吸道上皮细胞(HAEC)的原代培养,我们发现金黄色葡萄球菌主要黏附于未分化的HAEC,而对分化的HAEC的黏附较弱(低11至20倍)(P < 0.01)。一株缺乏纤连蛋白(FN)结合蛋白(FnBP)的金黄色葡萄球菌对未分化HAEC的黏附水平比亲本菌株低五倍(P < 0.005),这表明金黄色葡萄球菌的FN结合能力参与了对HAEC的黏附。我们还发现,从囊性纤维化患者(n = 18)和医院获得性肺炎患者(n = 14)的气道分泌物中分离出的32株金黄色葡萄球菌临床菌株中,97%含有两个fnb基因。肺炎患者的菌株比囊性纤维化患者的菌株具有显著更高(P < 0.05)的FN结合能力。通过Western配体亲和印迹法研究FnBPs的表达证实了这一结果。我们的结果表明FnBPs在金黄色葡萄球菌在气道定植中起主要作用,并指出黏附素调节途径在葡萄球菌感染过程中的重要性。