Adaptation of iron homeostasis pathways by a Pseudomonas aeruginosa pyoverdine mutant in the cystic fibrosis lung.

Adaptation of iron homeostasis pathways by a Pseudomonas aeruginosa pyoverdine mutant in the cystic fibrosis lung.
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囊性纤维化肺中铜绿假单胞菌pyoverdine突变体对铁稳态途径的适应。

DOI:
10.1128/jb.01491-14
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发表时间:
2014
影响因子:
3.2
通讯作者:
Oglesby-Sherrouse,AmandaG
Oglesby-Sherrouse,AmandaG
中科院分区:
生物学3区
文献类型:
--
作者:
Nguyen,AngelaT;O'Neill,MauraJ;Watts,AnnabelleM;Robson,CynthiaL;Lamont,IainL;Wilks,Angela;Oglesby-Sherrouse,AmandaG

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囊性纤维化(CF)患者患有慢性细菌性肺部感染,最显著的是铜绿假单胞菌,其在肺部持续数十年并经历广泛的演变。铜绿假单胞菌需要铁来产生毒力,并在急性感染期间使用荧光铁载体绿脓菌荧光素来固定和溶解三价铁。然而,绿脓杆菌荧光素突变体在一些CF患者的肺中积累,表明铜绿假单胞菌的血红素和亚铁获取途径在这种环境中更重要。在这里,我们试图通过使用纵向CF分离株来确定CF肺中铜绿假单胞菌的演变如何影响铁的获得和调节途径。这些分析表明,在几乎所有测试菌株的CF肺部感染过程中,铁载体的产生显著减少。这些菌株之一的质谱分析表明,后来的CF分离物通过HemO血红素加氧酶简化了细胞外血红素的代谢通量,导致更有效的血红素利用。此外,基因表达分析表明,铁调节通过PrrF小RNA(sRNA)的增强,在后来的CF分离。最后,对各种CF患者肺中铜绿假单胞菌基因表达的分析表明,PrrF和HemO在CF肺环境中一致表达。综合起来,这些结果表明,血红素是CF肺长期感染期间铁的关键来源,铁和血红素调节途径的变化在铜绿假单胞菌适应这种不断变化的宿主环境中起着至关重要的作用。
Cystic fibrosis (CF) patients suffer from chronic bacterial lung infections, most notably by Pseudomonas aeruginosa, which persists for decades in the lungs and undergoes extensive evolution. P. aeruginosa requires iron for virulence and uses the fluorescent siderophore pyoverdine to scavenge and solubilize ferric iron during acute infections. Pyoverdine mutants accumulate in the lungs of some CF patients, however, suggesting that the heme and ferrous iron acquisition pathways of P. aeruginosa are more important in this environment. Here, we sought to determine how evolution of P. aeruginosa in the CF lung affects iron acquisition and regulatory pathways through the use of longitudinal CF isolates. These analyses demonstrated a significant reduction of siderophore production during the course of CF lung infection in nearly all strains tested. Mass spectrometry analysis of one of these strains showed that the later CF isolate has streamlined the metabolic flux of extracellular heme through the HemO heme oxygenase, resulting in more-efficient heme utilization. Moreover, gene expression analysis shows that iron regulation via the PrrF small RNAs (sRNAs) is enhanced in the later CF isolate. Finally, analysis of P. aeruginosa gene expression in the lungs of various CF patients demonstrates that both PrrF and HemO are consistently expressed in the CF lung environment. Combined, these results suggest that heme is a critical source of iron during prolonged infection of the CF lung and that changes in iron and heme regulatory pathways play a crucial role in adaptation of P. aeruginosa to this ever-changing host environment.
DOI: 10.1099/mic.0.023531-0
发表时间: 2009-01-01
期刊: MICROBIOLOGY-SGM
影响因子: 2.8
作者:
Marshall, Bryan;Stintzi, Alain;Poole, Keith
通讯作者: Poole, Keith
DOI: 10.1128/iai.62.2.596-605.1994
发表时间: 1994-02-01
影响因子: 3.1
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影响因子: 3.1
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发表时间: 2004-06-29
影响因子: 11.1
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铜绿假单胞菌的氧和铁依赖性σ因子pvdS是实验性感染性心内膜炎的重要毒力因子。
DOI: 10.1086/315338
发表时间: 2000
期刊: The Journal of infectious diseases.
影响因子: --
作者:
Xiong,YQ;Vasil,ML;Johnson,Z;Ochsner,UA;Bayer,AS
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