McGuffie Bryan A, Vallet-Gely Isabelle, Dove Simon L
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
J Bacteriol. 2015 Nov 30;198(5):755-65. doi: 10.1128/JB.00784-15.
Pseudomonas aeruginosa is capable of causing a variety of acute and chronic infections. Here, we provide evidence that sbrR (PA2895), a gene previously identified as required during chronic P. aeruginosa respiratory infection, encodes an anti-σ factor that inhibits the activity of its cognate extracytoplasmic-function σ factor, SbrI (PA2896). Bacterial two-hybrid analysis identified an N-terminal region of SbrR that interacts directly with SbrI and that was sufficient for inhibition of SbrI-dependent gene expression. We show that SbrI associates with RNA polymerase in vivo and identify the SbrIR regulon. In cells lacking SbrR, the SbrI-dependent expression of muiA was found to inhibit swarming motility and promote biofilm formation. Our findings reveal SbrR and SbrI as a novel set of regulators of swarming motility and biofilm formation in P. aeruginosa that mediate their effects through muiA, a gene not previously known to influence surface-associated behaviors in this organism.
This study characterizes a σ factor/anti-σ factor system that reciprocally regulates the surface-associated behaviors of swarming motility and biofilm formation in the opportunistic pathogen Pseudomonas aeruginosa. We present evidence that SbrR is an anti-σ factor specific for its cognate σ factor, SbrI, and identify the SbrIR regulon in P. aeruginosa. We find that cells lacking SbrR are severely defective in swarming motility and exhibit enhanced biofilm formation. Moreover, we identify muiA (PA1494) as the SbrI-dependent gene responsible for mediating these effects. SbrIR have been implicated in virulence and in responding to antimicrobial and cell envelope stress. SbrIR may therefore represent a stress response system that influences the surface behaviors of P. aeruginosa during infection.
铜绿假单胞菌能够引发多种急性和慢性感染。在此，我们提供证据表明，sbrR（PA2895），一个先前被确定为在铜绿假单胞菌慢性呼吸道感染期间必需的基因，编码一种抗σ因子，该因子抑制其同源的胞外功能σ因子SbrI（PA2896）的活性。细菌双杂交分析确定了SbrR的一个N端区域，该区域直接与SbrI相互作用，并且足以抑制SbrI依赖的基因表达。我们表明SbrI在体内与RNA聚合酶结合，并鉴定了SbrIR调控子。在缺乏SbrR的细胞中，发现muiA的SbrI依赖表达抑制群体运动并促进生物膜形成。我们的研究结果揭示了SbrR和SbrI是铜绿假单胞菌群体运动和生物膜形成的一组新型调节因子，它们通过muiA介导其作用，muiA是一个以前未知会影响该生物体表面相关行为的基因。
本研究表征了一个σ因子/抗σ因子系统，该系统相互调节机会性病原体铜绿假单胞菌的群体运动和生物膜形成等表面相关行为。我们提供证据表明SbrR是其同源σ因子SbrI的特异性抗σ因子，并鉴定了铜绿假单胞菌中的SbrIR调控子。我们发现缺乏SbrR的细胞在群体运动方面存在严重缺陷，并表现出增强的生物膜形成。此外，我们鉴定出muiA（PA1494）是负责介导这些效应的SbrI依赖基因。SbrIR与毒力以及对抗菌和细胞包膜应激的反应有关。因此，SbrIR可能代表一种应激反应系统，在感染期间影响铜绿假单胞菌的表面行为。
