BsmR degrades c-di-GMP to modulate biofilm formation of nosocomial pathogen Stenotrophomonas maltophilia.
BsmR degrades c-di-GMP to modulate biofilm formation of nosocomial pathogen Stenotrophomonas maltophilia.
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DOI：
10.1038/s41598-017-04763-w
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发表时间：
2017-07-05
影响因子：
4.6
通讯作者：
Wang FF
中科院分区：
文献类型：
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作者：
Liu W;Tian XQ;Wei JW;Ding LL;Qian W;Liu Z;Wang FF
c-di-GMP是调节多种细菌过程的细胞第二信使，包括游动、生物膜形成和毒力。然而，在嗜麦芽窄食单胞菌，医院的病原体，经常感染免疫缺陷或免疫功能不全的患者，c-二-GMP的调节功能仍然不清楚。在这里，我们表明，BsmR是一个负调节生物膜的发展，降低c-di-GMP通过其EAL域。增加BsmR表达导致细菌游动的显著增加和细胞聚集的减少。BsmR调控至少349个基因的表达。其中，34个参与鞭毛组装和鞭毛组装相关转录因子（fsnR）的正调控。虽然BsmR是双组分信号系统的反应调节剂，但其在生物膜形成中的作用取决于其各自基因（bsmR）的表达水平，而不是蛋白质的磷酸化水平。转录因子BsmT的编码基因与bsmR位于同一个四顺反子操纵子中，研究表明它直接结合操纵子的启动子区域，并通过正调节环调节bsmR的转录。因此，我们的研究结果表明，c-di-GMP信号通路控制生物膜的形成和游泳在S。嗜麦芽窄食单胞菌，表明c-di-GMP信号传导作为开发抵抗这种病原体的新型抗菌剂的靶标。
c-di-GMP is a cellular second messenger that regulates diverse bacterial processes, including swimming, biofilm formation and virulence. However, in Stenotrophomonas maltophilia, a nosocomial pathogen that frequently infects immunodeficient or immunoincompetent patients, the regulatory function of c-di-GMP remains unclear. Here we show that BsmR is a negative regulator of biofilm development that degrades c-di-GMP through its EAL domain. Increasing BsmR expression resulted in significant increase in bacterial swimming and decrease in cell aggregation. BsmR regulates the expression of at least 349 genes. Among them, 34 involved in flagellar assembly and a flagellar-assembly-related transcription factor (fsnR) are positively regulated. Although BsmR is a response regulator of the two-component signaling system, its role in biofilm formation depends on the expression level of its respective gene (bsmR), not on the protein’s phosphorylation level. A transcription factor, BsmT, whose coding gene is located in the same tetra-cistronic operon as bsmR, was shown to directly bind to the promoter region of the operon and, through a positive regulatory loop, modulate bsmR transcription. Thus, our results revealed that the c-di-GMP signaling pathway controls biofilm formation and swimming in S. maltophilia, suggesting c-di-GMP signaling as a target in the development of novel antibacterial agents to resist this pathogen.