Linear tetrapyrroles and phytochrome-like sensors in signal transduction of the opportunistic pathogen Pseudomonas aeruginosa

这项建议侧重于研究线性四吡咯(Bilins)在细菌信号转导中的作用。对于许多病原菌，如铜绿假单胞菌，血红素是铁的重要来源。在吸收后，血红素分子被血红素加氧酶降解，产生铁、一氧化碳和胆绿素。血红素加氧酶PIGA只有在铁限制条件下才能诱导，这种非光合作用细菌的第二个可能的血红素加氧酶基因bphO出现在一个操纵子中，基因bphP编码一种细菌光敏色素。这项建议的主要目的是结合细菌光敏色素样传感器BphP，对两种血红素加氧酶和形成的胆绿素的功能进行表征。BphP在胆红素结合和传感中的作用，以及它在铜绿假单胞菌整个调控网络中对铁和血红素调控过程的贡献，将结合遗传学、生化和现代蛋白质组学和基因组学方法来确定。生物膜形成和感染的长期后果是普遍关注的问题。

This proposal focuses on the investigation of the role of linear tetrapyrroles (bilins) in bacterial signal transduction. For many pathogenic bacteria like Pseudomonas aeruginosa heme is an essential source of iron. After uptake, the heme molecule is degraded by heme oxygenases to yield iron, carbon monoxide and biliverdin. The heme oxygenase PigA is only induced under iron limiting conditions, the gene for a second putative heme oxygenase, bphO of this non-photosynthetic bacterium occurs in an operon with the gene bphP encoding a bacterial phytochrome. The major objective of this proposal is the functional characterization of the two heme oxygenases and the formed biliverdins in combination with the bacterial phytochrome-like sensor BphP. The role of BphP in bilin binding and sensing, and its contribution to iron- and heme regulated processes in the overall regulatory network of P. aeruginosa will be determined using a combination of genetic, biochemical and modern methods of proteomics and genomics. Long term consequences for biofilm formation and infection are of general interest.