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Overproduction of the AlgT Sigma Factor Is Lethal to Mucoid Pseudomonas aeruginosa.
Journal of Bacteriology ( IF 2.7 ) Pub Date : 2020-09-23 , DOI: 10.1128/jb.00445-20
Ashley R Cross 1, 2 , Vishnu Raghuram 1, 2 , Zihuan Wang 1, 2 , Debayan Dey 3 , Joanna B Goldberg 2, 4
Affiliation  

Pseudomonas aeruginosa isolates from chronic lung infections often overproduce alginate, giving rise to the mucoid phenotype. Isolation of mucoid strains from chronic lung infections correlates with a poor patient outcome. The most common mutation that causes the mucoid phenotype is called mucA22 and results in a truncated form of the anti-sigma factor MucA that is continuously subjected to proteolysis. When a functional MucA is absent, the cognate sigma factor, AlgT, is no longer sequestered and continuously transcribes the alginate biosynthesis operon, leading to alginate overproduction. In this work, we report that in the absence of wild-type MucA, providing exogenous AlgT is toxic. This is intriguing, since mucoid strains endogenously possess high levels of AlgT. Furthermore, we show that suppressors of toxic AlgT production have mutations in mucP, a protease involved in MucA degradation, and provide the first atomistic model of MucP. Based on our findings, we speculate that mutations in mucP stabilize the truncated form of MucA22, rendering it functional and therefore able to reduce toxicity by properly sequestering AlgT.

中文翻译:

AlgT Sigma因子的过度生产对铜绿假单胞菌假单胞菌是致命的。

来自慢性肺部感染的铜绿假单胞菌分离物通常会过量产生藻酸盐,从而产生粘液样表型。从慢性肺部感染中分离粘液样菌株与患者预后不良有关。导致粘液表型的最常见突变称为mucA22并产生截短形式的抗sigma因子MucA,将其连续进行蛋白水解。当缺少功能性MucA时,不再隔离同源的sigma因子AlgT,并连续转录藻酸盐的生物合成操纵子,从而导致藻酸盐的过量生产。在这项工作中,我们报告说,在没有野生型MucA的情况下,提供外源AlgT是有毒的。这很有趣,因为粘液样菌株内源性地具有高水平的AlgT。此外,我们表明有毒AlgT产生的抑制剂在mucP(一种参与MucA降解的蛋白酶)中具有突变,并提供了MucP的第一个原子模型。根据我们的发现,我们推测mucP中的突变 稳定MucA22的截短形式,使其具有功能性,因此能够通过适当隔离AlgT来降低毒性。
更新日期:2020-09-23
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