O'Dwyer Clíona A, Li Ming-Shi, Langford Paul R, Kroll J Simon
Molecular Infectious Diseases Group, Department of Paediatrics, Faculty of Medicine, Imperial College London, Wright-Fleming Institute, St Mary's Hospital Campus, Norfolk Place, London W2 1PG, UK.
Microbiology (Reading). 2009 Jun;155(Pt 6):1940-1952. doi: 10.1099/mic.0.026559-0. Epub 2009 Apr 21.
Neisseria meningitidis colonizes the human nasopharynx asymptomatically, often for prolonged periods, but occasionally invades from this site to cause life-threatening infection. In the nasopharynx aggregated organisms are closely attached to the epithelial surface, in a state in which the expression of components of the bacterial envelope differs significantly from that found in organisms multiplying exponentially in liquid phase culture or in the blood. We and others have hypothesized that here they are in the biofilm state, and to explore this we have investigated biofilm formation by the serogroup B strain MC58 on an abiotic surface, in a sorbarod system. Transcriptional changes were analysed, focusing on alteration in gene expression relevant to polysaccharide capsulation, lipooligosaccharide and outer-membrane protein synthesis - all phenotypes of importance in epithelial colonization. We report downregulation of genes controlling capsulation and the production of core oligosaccharide, and upregulation of genes encoding a range of outer-membrane components, reflecting phenotypic changes that have been established to occur in the colonizing state. A limited comparison with organisms recovered from an extended period of co-cultivation with epithelial cells suggests that this model system may better mirror natural colonization than do short-term meningococcal/epithelial cell co-cultivation systems. Modelling prolonged meningococcal colonization with a sorbarod system offers insight into gene expression during this important, but experimentally relatively inaccessible, phase of human infection.
脑膜炎奈瑟菌通常会在人类鼻咽部无症状地定植很长时间,但偶尔会从该部位侵入,引发危及生命的感染。在鼻咽部,聚集的细菌紧密附着在上皮表面,处于这种状态时,细菌包膜成分的表达与在液相培养或血液中指数增殖的细菌有显著差异。我们和其他人推测,它们在这里处于生物膜状态,为了探究这一点,我们研究了B群菌株MC58在一种非生物表面的山梨醇系统中形成生物膜的情况。分析了转录变化,重点关注与多糖荚膜、脂寡糖和外膜蛋白合成相关的基因表达变化——所有这些表型在上皮定植中都很重要。我们报告了控制荚膜形成和核心寡糖产生的基因下调,以及一系列外膜成分编码基因的上调,这反映了在定植状态下已确定发生的表型变化。与从与上皮细胞长期共培养中回收的细菌进行的有限比较表明,该模型系统可能比短期脑膜炎奈瑟菌/上皮细胞共培养系统更能反映自然定植情况。用山梨醇系统模拟脑膜炎奈瑟菌的长期定植,有助于深入了解人类感染这一重要但实验上相对难以研究的阶段中的基因表达情况。