Department of Pharmacy Practice, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
FEMS Microbiol Lett. 2009 Oct;299(1):100-9. doi: 10.1111/j.1574-6968.2009.01739.x. Epub 2009 Jul 27.
Among the different extracellular virulence factors produced by Pseudomonas aeruginosa are exotoxin A (ETA) and the pyoverdine and pyochelin siderophores. Production of ETA and the siderophores requires the function of the iron-starvation sigma factor PvdS, the transcriptional activator RegA, and the AraC-activator PchR. Iron represses the production of ETA and the siderophores by repressing the expression of pvdS, regA, and pchR. PvdS regulates the expression of the ETA gene, toxA, regA, and the pyoverdine synthesis genes. The catecholamine norepinephrine enhances the growth of pathogenic bacteria by transferring iron from host-binding proteins. In this study, we elucidated the mechanism by which norepinephrine and other catecholamines induce P. aeruginosa growth. We also investigated whether norepinephrine regulates the expression of toxA and the siderophore genes, and the mechanism of this regulation. Norepinephrine enhanced the growth of P. aeruginosa by supplying iron from transferrin. This provision of iron repressed the expression of toxA, the pyoverdine genes pvdD and pvdE, and their regulators, pvdS, regA, and pchR, suggesting that norepinephrine accomplishes this repression through PvdS and PchR. Additionally, norepinephrine bypassed PvdS and supported the growth of a pvdS deletion mutant, indicating that norepinephrine transfers iron to P. aeruginosa independent of pyoverdine. Thus, norepinephrine apparently influences the pathogenesis of P. aeruginosa by affecting its pattern of growth and the production of virulence factors.
在铜绿假单胞菌产生的不同细胞外毒力因子中，有外毒素 A（ETA）和绿色菌素和焦脱铁素铁载体。ETA 和铁载体的产生需要缺铁应激σ因子 PvdS、转录激活因子 RegA 和 AraC 激活因子 PchR 的功能。铁通过抑制 pvdS、regA 和 pchR 的表达来抑制 ETA 和铁载体的产生。PvdS 调节 ETA 基因、toxA、regA 和绿色菌素合成基因的表达。儿茶酚胺去甲肾上腺素通过从宿主结合蛋白中转移铁来增强病原菌的生长。在这项研究中，我们阐明了去甲肾上腺素和其他儿茶酚胺诱导铜绿假单胞菌生长的机制。我们还研究了去甲肾上腺素是否调节 toxA 和铁载体基因的表达，以及这种调节的机制。去甲肾上腺素通过从转铁蛋白中提供铁来增强铜绿假单胞菌的生长。这种铁的供应抑制了 toxA、绿色菌素基因 pvdD 和 pvdE 及其调节剂 pvdS、regA 和 pchR 的表达，表明去甲肾上腺素通过 PvdS 和 PchR 实现这种抑制。此外，去甲肾上腺素绕过 PvdS 并支持 pvdS 缺失突变体的生长，表明去甲肾上腺素将铁转递给铜绿假单胞菌独立于绿色菌素。因此，去甲肾上腺素显然通过影响其生长模式和毒力因子的产生来影响铜绿假单胞菌的发病机制。
