Department of Sciences, University 'Roma Tre', Rome, Italy.
Environ Microbiol. 2014 Mar;16(3):676-88. doi: 10.1111/1462-2920.12164. Epub 2013 Jun 25.
Pseudomonas aeruginosa is a versatile bacterial pathogen capable of occupying diverse ecological niches. To cope with iron limitation, P. aeruginosa secretes two siderophores, pyoverdine and pyochelin, whose ability to deliver iron to the cell is crucial for biofilm formation and pathogenicity. In this study, we describe a link between iron uptake and the Gac/Rsm system, a conserved signal transducing pathway of P. aeruginosa that controls the production of extracellular products and virulence factors, as well as the switch from planktonic to biofilm lifestyle. We have observed that pyoverdine and pyochelin production in P. aeruginosa is strongly dependent on the activation state of the Gac/Rsm pathway, which controls siderophore regulatory and biosynthetic genes at the transcriptional level, in a manner that does not involve regulation of ferric uptake regulator (Fur) expression. Gac/Rsm-mediated regulation of iron uptake genes appears to be conserved in different P. aeruginosa strains. Further experiments led to propose that the Gac/Rsm system regulates siderophore production through modulation of the intracellular levels of the second messenger c-di-GMP, indicating that the c-di-GMP and the Gac/Rsm regulatory networks essential for biofilm formation can also coordinately control iron uptake in P. aeruginosa.
铜绿假单胞菌是一种多功能的细菌病原体，能够占据多种生态位。为了应对铁限制，铜绿假单胞菌分泌两种铁载体，即绿脓菌素和焦脱镁叶绿酸，它们将铁输送到细胞内的能力对于生物膜形成和致病性至关重要。在这项研究中，我们描述了铁摄取与 Gac/Rsm 系统之间的联系，Gac/Rsm 系统是铜绿假单胞菌保守的信号转导途径，它控制着细胞外产物和毒力因子的产生，以及从浮游生物到生物膜生活方式的转变。我们观察到，铜绿假单胞菌中绿脓菌素和焦脱镁叶绿酸的产生强烈依赖于 Gac/Rsm 途径的激活状态，该途径在转录水平上控制着铁载体调节和生物合成基因，而不涉及铁摄取调节因子 (Fur) 表达的调节。Gac/Rsm 介导的铁摄取基因的调节似乎在不同的铜绿假单胞菌菌株中是保守的。进一步的实验表明，Gac/Rsm 系统通过调节细胞内第二信使 c-di-GMP 的水平来调节铁载体的产生，这表明 c-di-GMP 和 Gac/Rsm 调节网络对于生物膜形成是必不可少的，它们也可以协调控制铜绿假单胞菌中的铁摄取。
