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Condensins are essential for Pseudomonas aeruginosa corneal virulence through their control of lifestyle and virulence programs
Molecular Microbiology ( IF 3.6 ) Pub Date : 2022-01-24 , DOI: 10.1111/mmi.14883
Hang Zhao 1 , April L Clevenger 1 , Phillip S Coburn 2 , Michelle C Callegan 2 , Valentin V Rybenkov 1
Affiliation  

Pseudomonas aeruginosa is a significant opportunistic pathogen responsible for numerous human infections. Its high pathogenicity resides in a diverse array of virulence factors and an ability to adapt to hostile environments. We report that these factors are tied to the activity of condensins, SMC and MksBEF, which primarily function in structural chromosome maintenance. This study revealed that both proteins are required for P. aeruginosa virulence during corneal infection. The reduction in virulence was traced to broad changes in gene expression. Transcriptional signatures of smc and mksB mutants were largely dissimilar and non-additive, with the double mutant displaying a distinct gene expression profile. Affected regulons included those responsible for lifestyle control, primary metabolism, surface adhesion and biofilm growth, iron and sulfur assimilation, and numerous virulence factors, including type 3 and type 6 secretion systems. The in vitro phenotypes of condensin mutants mirrored their transcriptional profiles and included impaired production and secretion of multiple virulence factors, growth deficiencies under nutrient limiting conditions, and altered c-di-GMP signaling. Notably, c-di-GMP mediated some but not all transcriptional responses of the mutants. Thus, condensins are integrated into the control of multiple genetic programs related to epigenetic and virulent behavior of P. aeruginosa.

中文翻译:

凝缩素通过控制生活方式和毒力程序对铜绿假单胞菌角膜毒力至关重要

铜绿假单胞菌是一种重要的机会性病原体,可导致许多人类感染。其高致病性存在于多种毒力因子和适应恶劣环境的能力。我们报告这些因素与凝缩蛋白、SMC 和 MksBEF 的活性有关,它们主要在结构染色体维护中发挥作用。这项研究表明,角膜感染期间铜绿假单胞菌的毒力需要这两种蛋白质。毒力的降低可追溯到基因表达的广泛变化。smcmksB的转录特征突变体在很大程度上是不同的和非加性的,双突变体显示出不同的基因表达谱。受影响的调节子包括那些负责生活方式控制、初级代谢、表面粘附和生物膜生长、铁和硫同化以及许多毒力因子(包括 3 型和 6 型分泌系统)的调节子。凝聚素突变体的体外表型反映了它们的转录谱,包括多种毒力因子的产生和分泌受损、营养限制条件下的生长缺陷以及 c-di-GMP 信号传导的改变。值得注意的是,c-di-GMP 介导了突变体的一些但不是所有的转录反应。因此,凝缩蛋白被整合到与表观遗传和毒力行为相关的多个遗传程序的控制中。铜绿假单胞菌
更新日期:2022-01-24
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