Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa.

Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa.
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DOI:
10.1111/j.1365-2958.2012.08049.x
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发表时间:
2012-05
影响因子:
3.6
通讯作者:
Goldberg JB
Goldberg JB
中科院分区:
生物学2区
文献类型:
--
作者:
Damron FH;Goldberg JB

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铜绿假单胞菌是一种革兰氏阴性菌,是一种重要的机会致病菌,与皮肤和软组织感染、医院获得性肺炎和败血症有关。此外,它可以长期定植于囊性纤维化(CF)患者的肺部。被称为藻酸盐的胞外多糖的过量生产为铜绿假单胞菌提供了选择性优势,并促进了在CF肺中的存活。在固体培养基上观察到的藻酸盐过量生产的体外表型被称为粘液。藻酸盐机器和生物合成酶的表达由细胞质外σ因子σ22(AlgU/T)控制。σ22活性和类粘蛋白表型的关键负调节因子是同源抗σ因子MucA。MucA将σ22螯合到内膜,抑制σ因子的转录活性。转变为粘液样表型的充分研究的机制是mucA突变,导致MucA功能丧失,因此激活σ22。最近,调节性膜内蛋白水解(RIP)已被认为是抗σ因子MucA的蛋白水解导致活性σ22的机制,从而允许铜绿假单胞菌通过过量产生藻酸盐来响应环境应激条件。这篇综述的目的是阐明已经确定和提出的导致RIP的途径。
Pseudomonas aeruginosa, a Gram-negative bacterium, is a significant opportunistic pathogen associated with skin and soft tissue infections, nosocomial pneumonia, and sepsis. In addition, it can chronically colonize the lungs of cystic fibrosis (CF) patients. Overproduction of the exopolysaccharide called alginate provides P. aeruginosa with a selective advantage and facilitates survival in the CF lung. The in vitro phenotype of alginate overproduction observed on solid culture media is referred to as mucoid. Expression of the alginate machinery and biosynthetic enzymes are controlled by the extracytoplasmic sigma factor, σ22 (AlgU/T). The key negative regulator of both σ22 activity and the mucoid phenotype is the cognate anti-sigma factor MucA. MucA sequesters σ22 to the inner membrane inhibiting the sigma factor’s transcriptional activity. The well-studied mechanism for transition to the mucoid phenotype is mutation of mucA, leading to loss of MucA function and therefore activation of σ22. Recently, regulated intramembrane proteolysis (RIP) has been recognized as a mechanism whereby proteolysis of the anti-sigma factor MucA leads to active σ22 allowing P. aeruginosa to respond to environmental stress conditions by overproduction of alginate. The goal of this review is to illuminate the pathways leading to RIP that have been identified and proposed.
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