The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa

The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa
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DOI:
10.1099/mic.0.024554-0
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发表时间:
2009-03-01
期刊:
影响因子:
2.8
通讯作者:
Hancock, Robert E. W.
Hancock, Robert E. W.
中科院分区:
生物学4区
文献类型:
--
作者:
Gooderham, W. James;Gellatly, Shaan L.;Hancock, Robert E. W.

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铜绿假单胞菌是一种普遍存在的环境革兰氏阴性菌,也是院内感染和囊性纤维化慢性肺部感染的主要人类机会致病菌。PhoP-PhoQ是一个双组分调控系统,已被鉴定为在其他几种革兰氏阴性菌中对毒力和阳离子抗菌肽抗性至关重要。这项研究表明,phoQ的突变导致减少抽搐运动,生物膜的形成和快速附着到表面,2.2倍减少对人类肺上皮细胞的细胞毒性,大幅降低莴苣叶的毒力,和一个主要的,10000倍减少在慢性大鼠肺部感染的竞争力。微阵列分析显示,PhoQ控制许多基因的表达,这些基因与这些表型及其在多粘菌素B耐药性中的已知作用一致。也证明了PhoQ控制已知PhoP调节子之外的许多基因的表达。
Pseudomonas aeruginosa is a ubiquitous environmental Gram-negative bacterium that is also a major opportunistic human pathogen in nosocomial infections and cystic fibrosis chronic lung infections. PhoP-PhoQ is a two-component regulatory system that has been identified as essential for virulence and cationic antimicrobial peptide resistance in several other Gram-negative bacteria. This study demonstrated that mutation of phoQ caused reduced twitching motility, biofilm formation and rapid attachment to surfaces, 2.2-fold reduced cytotoxicity to human lung epithelial cells, substantially reduced lettuce leaf virulence, and a major, 10000-fold reduction in competitiveness in chronic rat lung infections. Microarray analysis revealed that PhoQ controlled the expression of many genes consistent with these phenotypes and with its known role in polymyxin B resistance. It was also demonstrated that PhoQ controls the expression of many genes outside the known PhoP regulon.