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

本文主要研究线性四吡咯（胆磷脂）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。摄取后，血红素分子被血红素加氧酶降解，生成铁、一氧化碳和胆绿素。血红素加氧酶PigA仅在铁限制条件下被诱导，这种非光合细菌的第二种假定的血红素加氧酶bphO基因发生在编码细菌光敏色素的基因bphP的操纵子中。本研究的主要目的是研究两种血红素加氧酶的功能特征，以及与细菌光敏色素样传感器BphP结合形成的胆绿素。BphP在十亿蛋白结合和传感中的作用，以及它在铜绿假单胞菌整体调控网络中对铁和血红素调控过程的贡献，将通过遗传、生化和蛋白质组学和基因组学的现代方法来确定。生物膜形成和感染的长期后果是人们普遍感兴趣的。

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.