Kang Donghoon, Turner Kelly E, Kirienko Natalia V
Department of Biosciences, Rice University, Houston, TX 77005, USA.
Pathogens. 2017 Dec 25;7(1):3. doi: 10.3390/pathogens7010003.
Biofilms create an impermeable barrier against antimicrobial treatment and immune cell access, severely complicating treatment and clearance of nosocomial infections. We recently reported that biofilm also contributes to pathogen virulence by regulating the production of the siderophore pyoverdine. In this study, we investigated the role of PqsA, a key cell-signaling protein, in this regulatory pathway. We demonstrate that PqsA promotes pyoverdine production in a biofilm-dependent manner. Under nutritionally deficient conditions, where biofilm and pyoverdine are decoupled, PqsA is dispensable for pyoverdine production. Interestingly, although PqsA-dependent pyoverdine production does not rely upon Pseudomonas quinolone signal (PQS) biosynthesis, exogenous PQS can also trigger biofilm-independent production of pyoverdine. Adding PQS rapidly induced planktonic cell aggregation. Moreover, these clumps of cells exhibit strong expression of pyoverdine biosynthetic genes and show substantial production of this siderophore. Finally, we surveyed the relationship between biofilm formation and pyoverdine production in various clinical and environmental isolates of to evaluate the clinical significance of targeting biofilm during infections. Our findings implicate PqsA in virulence by regulating biofilm formation and pyoverdine production.
生物膜形成了一道对抗菌治疗和免疫细胞进入的不可渗透屏障,严重使医院感染的治疗和清除复杂化。我们最近报道,生物膜还通过调节铁载体绿脓菌素的产生来促进病原体的毒力。在本研究中,我们调查了关键细胞信号蛋白PqsA在该调节途径中的作用。我们证明PqsA以生物膜依赖性方式促进绿脓菌素的产生。在营养缺乏条件下,生物膜和绿脓菌素解偶联,PqsA对于绿脓菌素的产生是可有可无的。有趣的是,尽管依赖PqsA的绿脓菌素产生不依赖于铜绿假单胞菌喹诺酮信号(PQS)的生物合成,但外源性PQS也可以触发不依赖生物膜的绿脓菌素产生。添加PQS会迅速诱导浮游细胞聚集。此外,这些细胞团表现出绿脓菌素生物合成基因的强烈表达,并显示出这种铁载体的大量产生。最后,我们调查了各种临床和环境分离株中生物膜形成与绿脓菌素产生之间的关系,以评估感染期间靶向生物膜的临床意义。我们的研究结果表明PqsA通过调节生物膜形成和绿脓菌素产生参与了毒力作用。