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首页> 外文期刊>Journal of bacteriology >Pseudomonas aeruginosa Rugose Small-Colony Variants Have Adaptations That Likely Promote Persistence in the Cystic Fibrosis Lung
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Pseudomonas aeruginosa Rugose Small-Colony Variants Have Adaptations That Likely Promote Persistence in the Cystic Fibrosis Lung

机译:铜绿假单胞菌毛状小菌落变种可能会促进囊性纤维化肺的持久性

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摘要

Pseudomonas aeruginosa is recognized for its ability to colonize diverse habitats, ranging from soil to immunocompromised people. The formation of surface-associated communities called biofilms is one factor thought to enhance colonization and persistence in these diverse environments. Another factor is the ability of P. aeruginosa to diversify genetically, generating phenotypically distinct subpopulations. One manifestation of diversification is the appearance of colony morphology variants on solid medium. Both laboratory biofilm growth and chronic cystic fibrosis (CF) airway infections produce rugose small-colony variants (RSCVs) characterized by wrinkled, small colonies and an elevated capacity to form biofilms. Previous reports vary on the characteristics attributable to RSCVs. Here we report a detailed comparison of clonally related wild-type and RSCV strains isolated from both CF sputum and laboratory biofilm cultures. The clinical RSCV had many characteristics in common with biofilm RSCVs. Transcriptional profiling and Biolog phenotypic analysis revealed that RSCVs display increased expression of the pel and psl polysaccharide gene clusters, decreased expression of motility functions, and a defect in growth on some amino acid and tricarboxylic acid cycle intermediates as sole carbon sources. RSCVs also elicited a reduced chemokine response from polarized airway epithelium cells compared to wild-type strains. A common feature of all RSCVs analyzed in this study is increased levels of the intracellular signaling molecule cyclic di-GMP (c-di-GMP). To assess the global transcriptional effects of elevated c-di-GMP levels, we engineered an RSCV strain that had elevated c-di-GMP levels but did not autoaggregate. Our results showed that about 50 genes are differentially expressed in response to elevated intracellular c-di-GMP levels. Among these genes are the pel and psl genes, which are upregulated, and flagellum and pilus genes, which are downregulated. RSCV traits such as increased exopolysaccharide production leading to antibiotic tolerance, altered metabolism, and reduced immunogenicity may contribute to increased persistence in biofilms and in the airways of CF lungs.
机译:铜绿假单胞菌(Pseudomonas aeruginosa)因其能够在从土壤到免疫力低下的人不同的栖息地定殖的能力而闻名。被称为生物膜的与表面相关的群落的形成是增强这些不同环境中定植和持久性的一个因素。另一个因素是 P的能力。铜绿假单胞菌在遗传上多样化,产生表型上不同的亚群。多样化的一种表现是在固体培养基上出现菌落形态变异。实验室生物膜生长和慢性囊性纤维化(CF)气道感染都会产生皱纹小菌落变体(RSCV),其特征是皱纹,小菌落和形成生物膜的能力提高。以前的报告对归因于RSCV的特征有所不同。在这里,我们报告从CF痰和实验室生物膜培养物中分离出的克隆相关野生型和RSCV菌株的详细比较。临床RSCV具有许多与生物膜RSCV相同的特征。转录谱和Biolog表型分析表明RSCVs显示 pel psl 多糖基因簇的表达增加,运动功能的表达减少,并且某些氨基酸的生长缺陷和三羧酸循环中间体作为唯一碳源。与野生型菌株相比,RSCV还引起极化气道上皮细胞趋化因子反应的降低。在这项研究中分析的所有RSCV的一个共同特征是细胞内信号分子环状di-GMP(c-di-GMP)的水平升高。为了评估c-di-GMP水平升高的总体转录效应,我们设计了一个cc-di-GMP水平升高但没有自动聚集的RSCV菌株。我们的结果表明,约有50个基因在细胞内c-di-GMP水平升高时有所差异。这些基因中有上调的 pel psl 基因,以及下调的鞭毛和菌毛基因。 RSCV特征,如增加的胞外多糖产量导致抗生素耐受性,代谢改变和免疫原性降低,可能会导致生物膜和CF肺气道中的持久性增加。

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