Hassett Daniel J, Cuppoletti John, Trapnell Bruce, Lymar Sergei V, Rowe John J, Yoon Sang Sun, Hilliard George M, Parvatiyar Kislay, Kamani Moneesha C, Wozniak Daniel J, Hwang Sung Hei, McDermott Timothy R, Ochsner Urs A
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA.
Adv Drug Deliv Rev. 2002 Dec 5;54(11):1425-43. doi: 10.1016/s0169-409x(02)00152-7.
Recent evidence indicates that Pseudomonas aeruginosa residing as biofilms in airway mucus of cystic fibrosis (CF) patients is undergoing anaerobic metabolism, a form of growth requiring gene products that are not utilized during aerobic growth. The outer membrane protein, OprF, and the rhl quorum sensing circuit are two previously unrecognized cellular factors that are required for optimal anaerobic biofilm viability. Without OprF, bacteria grow extremely poorly because they lack nitrite reductase activity while lacking rhlR or rhlI forces bacteria to undergo metabolic suicide by overproduction of nitric oxide. Furthermore, anaerobic growth favors maintenance of the mucoid, alginate-overproducing phenotype. Thus, with increasing age of CF patients, mucoid populations predominate, indicating that anaerobic bacteria reside in the inspissated airway mucus. Because many frontline antibiotics used in the treatment of CF airway disease are either ineffective or show reduced efficacy during anaerobic conditions, we propose development of new drugs to combat anaerobic metabolism by P. aeruginosa for more effective treatment of chronic CF lung infections.
最近的证据表明，在囊性纤维化（CF）患者气道黏液中以生物膜形式存在的铜绿假单胞菌正在进行厌氧代谢，这种生长形式需要一些在有氧生长过程中不被利用的基因产物。外膜蛋白OprF和rhl群体感应回路是两个以前未被认识的细胞因子，它们是厌氧生物膜最佳生存能力所必需的。没有OprF，细菌生长极其缓慢，因为它们缺乏亚硝酸还原酶活性，而缺乏rhlR或rhlI会迫使细菌因一氧化氮过量产生而进行代谢自杀。此外，厌氧生长有利于维持黏液样、过量产生藻酸盐的表型。因此，随着CF患者年龄的增长，黏液样菌群占主导地位，这表明厌氧细菌存在于浓缩的气道黏液中。由于用于治疗CF气道疾病的许多一线抗生素在厌氧条件下要么无效，要么疗效降低，我们建议开发新药来对抗铜绿假单胞菌的厌氧代谢，以便更有效地治疗慢性CF肺部感染。
