Sriramulu Dinesh D, Lünsdorf Heinrich, Lam Joseph S, Römling Ute
Microbiology and Tumor Biology Center (MTC), Karolinska Institutet, 17177 Stockholm, Sweden 2,3Department of Cell Biology and Immunology2 and Department of Microbiology3, Gesellschaft für Biotechnologische Forschung, 38124 Braunschweig, Germany 4Department of Microbiology, University of Guelph, Canada N1G2W1.
J Med Microbiol. 2005 Jul;54(Pt 7):667-676. doi: 10.1099/jmm.0.45969-0.
Pseudomonas aeruginosa colonizing the lung of cystic fibrosis patients is responsible for a decline in health and poor prognosis for these patients. Once established, growth of P. aeruginosa in microcolonies makes it very difficult to eradicate the organisms by antimicrobial treatment. An artificial sputum medium was developed to mimic growth of P. aeruginosa in the cystic fibrosis lung habitat and it was found that the organisms grew in tight microcolonies attached to sputum components. Several genes, such as algD, oprF and lasR but not fliC, were required for tight microcolony formation. Among the sputum components, amino acids, lecithin, DNA, salt and low iron were required for tight microcolony formation. Amino acids were also shown to be responsible for various other cystic-fibrosis-specific phenotypes of P. aeruginosa, such as diversification of colony morphology, alterations in LPS structure and hyperexpression of OprF. Since the amino acid content of sputum is elevated in severe lung disease, it is suggested that the tight microcolony biofilm is maintained in these conditions and that they contribute to the vicious cycle of disease severity and failure to eradicate the organism. Thus, growth of P. aeruginosa in artificial sputum medium is an appropriate model of chronic lung colonization and may be useful for evaluating therapeutic procedures and studying antibiotic-resistance mechanisms.
定殖于囊性纤维化患者肺部的铜绿假单胞菌会导致这些患者健康状况下降和预后不良。一旦定殖，铜绿假单胞菌在微菌落中的生长使得通过抗菌治疗根除这些微生物变得非常困难。开发了一种人工痰液培养基来模拟铜绿假单胞菌在囊性纤维化肺部环境中的生长，结果发现这些微生物在附着于痰液成分的紧密微菌落中生长。紧密微菌落形成需要几个基因，如algD、oprF和lasR，但不需要fliC。在痰液成分中，紧密微菌落形成需要氨基酸、卵磷脂、DNA、盐和低铁。氨基酸还被证明与铜绿假单胞菌的各种其他囊性纤维化特异性表型有关，如菌落形态的多样化、脂多糖结构的改变和OprF的过度表达。由于严重肺部疾病中痰液的氨基酸含量升高，提示在这些情况下紧密微菌落生物膜得以维持，并且它们促成了疾病严重程度和无法根除该微生物的恶性循环。因此，铜绿假单胞菌在人工痰液培养基中的生长是慢性肺部定殖的合适模型，可能有助于评估治疗程序和研究抗生素耐药机制。
