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Abstract：
Pseudomonas aeruginosa is one of the leading causes of nosocomial infections worldwide and has emerged as a serious public health threat, due in large part to its multiple virulence factors and remarkable resistance capabilities. Stk1, a eukaryotic-type Ser/Thr protein kinase, has been shown in our previous work to be involved in the regulation of several signalling pathways and biological processes. Here, we demonstrate that deletion of stk1 leads to alterations in several virulence- and resistance-related physiological functions, including reduced pyocyanin and pyoverdine production, attenuated twitching motility, and enhanced biofilm production, extracellular polysaccharide secretion, and antibiotic resistance. Moreover, we identified AlgR, an important transcriptional regulator, as a substrate for Stk1, with its phosphorylation at the Ser143 site catalysed by Stk1. Intriguingly, both the deletion of stk1 and the mutation of Ser143 of AlgR to Ala result in similar changes in the above-mentioned physiological functions. Furthermore, assays of algR expression in these strains suggest that changes in the phosphorylation state of AlgR, rather than its expression level, underlie changes in these physiological functions. These findings uncover Stk1-mediated phosphorylation of AlgR as an important mechanism for regulating virulence and resistance in P. aeruginosa.
摘要：
铜绿假单胞菌是全球范围内引起医院感染的主要原因之一，已成为严重的公共卫生威胁，在很大程度上是由于其多重毒力因子和显著的抗性能力。Stk1，一种真核类型的Ser/Thr蛋白激酶，在我们以前的工作中已经显示出参与几种信号通路和生物过程的调节。这里,我们证明了stk1的缺失导致几种与病毒和抗性相关的生理功能的改变，包括减少的绿脓苷和焦啶的产生，减弱的抽搐运动，和增强生物膜的生产，胞外多糖分泌，抗生素耐药性。此外，我们确认了AlgR,一个重要的转录调节因子，作为Stk1的底物，其在Ser143位点的磷酸化由Stk1催化。有趣的是，stk1的缺失和AlgR的Ser143突变为Ala导致上述生理功能的类似变化。此外，这些菌株中algR表达的测定表明，AlgR磷酸化状态的变化，而不是它的表达水平，这些生理功能的变化。这些发现揭示了Stk1介导的AlgR磷酸化是调节铜绿假单胞菌毒力和抗性的重要机制。
