The P. aeruginosa Heme Binding Protein PhuS Is a Heme Oxygenase Titratable Regulator of Heme Uptake
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- 作者：Maura J. O鈥橬eill ; Angela Wilks
- 刊名：ACS Chemical Biology
- 出版年：2013
- 出版时间：August 16, 2013
- 年：2013
- 卷：8
- 期：8
- 页码：1794-1802
- 全文大小：490K
- 年卷期：v.8,no.8(August 16, 2013)
- ISSN：1554-8937
文摘
The Pseudomonas aeruginosa heme utilization (Phu) system encodes several proteins involved in the acquisition of heme as an iron source. Once internalized, heme is degraded by the iron-regulated heme oxygenase, HemO to biliverdin (BV) IX未 and 尾. In vitro studies have shown holo-PhuS transfers heme to the iron-regulated HemO. This protein鈥損rotein interaction is specific for HemO as PhuS does not interact with the 伪-regioselective heme oxygenase, BphO. Bacterial genetics and isotopic labeling (13C-heme) studies confirmed extracellular heme is converted to 13C-BVIX 未 and 尾 through the catalytic action of HemO. In an effort to further understand the role of PhuS, similar studies were performed on the P. aeruginosa PAO1 螖phuS and 螖phuS/螖hemO strains. In contrast to wild-type strain, the absence of PhuS results in extracellular heme uptake and degradation via the catalytic action of HemO and BphO. At low heme concentrations, loss of PhuS leads to inefficient extracellular heme uptake supported by the fact the mRNA levels of PhuR, HemO, and BphO remain elevated when compared to the wild-type PAO1. On increasing extracellular heme concentrations, the elevated levels of PhuR, HemO, and BphO allow 鈥渓eaky uptake鈥?and degradation of heme via HemO and BphO. Similarly, in the 螖phuS/螖hemO strain, the higher heme concentrations combined with elevated levels of PhuR and BphO leads to nonspecific heme uptake and degradation by BphO. Thus we propose heme flux into the cell is driven by the catalytic action of HemO with PhuS acting as a 鈥渃ontrol valve鈥?to regulate extracellular heme flux.