The two-component system TarR-TarS is regulated by c-di-GMP/FleQ and FliA and modulates antibiotic susceptibility in Pseudomonas putida.

The two-component system TarR-TarS is regulated by c-di-GMP/FleQ and FliA and modulates antibiotic susceptibility in Pseudomonas putida.
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双组分系统 TarR-TarS 受 c-di-GMP/FleQ 和 FliA 调节,并调节恶臭假单胞菌的抗生素敏感性。

DOI:
10.1111/1462-2920.15555
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发表时间:
2021-05
影响因子:
5.1
通讯作者:
Qiaoyun Huang
Qiaoyun Huang
中科院分区:
生物学2区
文献类型:
--
作者:
Yujie Xiao;Liang Nie;Haozhe Chen;Meina He;Qingyuan Liang;Hailing Nie;Wenli Chen;Qiaoyun Huang

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双组分系统(TCS)是细菌感知和响应环境信号的主要方式。恶臭假单胞菌基因组包含数十个编码TCS的基因,但这些基因的表型-基因相关性和转录调控在很大程度上是未知的。在此,我们对一个保守的恶臭假单胞菌TCS的功能和转录调控进行了研究,命名为Tarr-Tars。TARS(PP_0769)编码一个潜在的组氨酸激酶,而TARR(PP_0768)编码一个潜在的反应调节因子。蛋白质相互作用实验和磷酸化实验证实TARR-TARS是一种功能性TCS。在抗生素作用下的生长实验表明,Tarr-Tars对细菌对多种抗生素的耐药性有正向调节作用。下拉实验表明,TARR与假想蛋白PP_0800和伴侣蛋白GroEL直接相互作用。GroEL对抗生素耐药有积极作用,而PP_0800对抗生素耐药性无明显影响。调节因子FleQ间接激活Tarr-Tars转录。然而,第二信使c-di-GMP拮抗FleQ的激活,从而抑制Tarr-tars的转录。Sigma因子FliA通过一个一致的基序直接激活Tarr-Tars转录。这些发现揭示了Tarr-tars的功能和转录调控,丰富了恶臭螺旋体c-di-GMP与抗生素耐药性关系的知识。
Two-component systems (TCSs) are predominant means by which bacteria sense and respond to environment signals. Genome of Pseudomonas putida contains dozens of putative TCS-encoding genes, but phenotypical-genotypical correlation and transcriptional regulation of these genes are largely unknown. Herein, we characterized function and transcriptional regulation of a conserved P. putida TCS, named TarR-TarS. TarS (PP_0769) encodes a potential histidine kinase, and tarR (PP_0768) encodes a potential response regulator. Protein-protein interaction assay and phosphorylation assay confirmed that TarR-TarS was a functional TCS. Growth assay under antibiotics revealed that TarR-TarS positively regulated bacterial resistance to multiple antibiotics. Pull-down assay revealed that TarR directly interacted with PP_0800 (a hypothetical protein) and GroEL (the chaperonin). GroEL played a positive role in antibiotic resistance, while PP_0800 seemed to have no effect on antibiotic resistance. The regulator FleQ indirectly activated tarR-tarS transcription. However, the second messenger c-di-GMP antagonized FleQ activation to inhibit tarR-tarS transcription. The sigma factor FliA directly activated tarR-tarS transcription via a consensus motif. These findings reveal function and transcriptional regulation of TarR-TarS, and enrich knowledge regarding the relationship between c-di-GMP and antibiotic resistance in P. putida.
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