GPI0363 inhibits the interaction of RNA polymerase with DNA in Staphylococcus aureus

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GPI0363 inhibits the interaction of RNA polymerase with DNA in Staphylococcus aureus

机译：GPI0363抑制RNA聚合酶与DNA在金黄色葡萄球菌中的相互作用

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We previously reported a therapeutically effective spiro-heterocyclic compound, GPI0363, that inhibits the transcription of Staphylococcus aureus via the primary sigma factor of RNA polymerase, SigA. Here, we demonstrated that GPI0363 shares no cross-resistance with the clinically used RNA polymerase inhibitors rifampicin and fidaxomicin. Furthermore, we found that GPI0363 bound to SigA of both GPI0363-susceptible and resistant strains, and inhibited the interaction of the RNA polymerase holoenzyme with DNA. In addition, the gene expression patterns following GPI0363 treatment were different from those following rifampicin treatment. These findings suggest that GPI0363 has a unique mechanism of action and can serve as a promising lead molecule to develop staphylococcal RNA polymerase inhibitors.

机译：我们之前报道了一种治疗有效的螺杂环化合物GPI0363，其抑制了通过RNA聚合酶，SIGA的初级Sigma因子转录葡萄球菌。在这里，我们证明GPI0363与临床使用的RNA聚合酶抑制剂利福平和Fidaxomicin共享交叉阻力。此外，我们发现GPI0363与GPI0363易感和抗性菌株的SIGA结合，并抑制RNA聚合酶全酶与DNA的相互作用。此外，GPI0363处理后的基因表达模式与下列比利福平治疗后的基因表达模式不同。这些发现表明GPI0363具有独特的作用机制，可以作为有前途的铅分子，以开发葡萄球菌RNA聚合酶抑制剂。

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《RSC Advances》 |2019年第65期|共6页
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1. GPI0363 inhibits the interaction of RNA polymerase with DNA in Staphylococcus aureus [J] . RSC Advances . 2019,第65期

机译：GPI0363抑制RNA聚合酶与DNA在金黄色葡萄球菌中的相互作用
2. Sigma-B, a putative operon encoding alternate sigma factor of Staphylococcus aureus RNA polymerase: molecular cloning and DNA sequencing. [J] . S Wu, H de Lencastre, A Tomasz Journal of bacteriology . 1996,第20期

机译：Sigma-B，一种假定的操纵子，编码金黄色葡萄球菌RNA聚合酶的另一个σ因子：分子克隆和DNA测序。
3. Novel non-nucleobase inhibitors of Staphylococcus aureus DNA polymerase IIIC. [J] . Rose Y, Ciblat S, Reddy R, Bioorganic and Medicinal Chemistry Letters . 2006,第4期

机译：金黄色葡萄球菌DNA聚合酶IIIC的新型非核碱基抑制剂。
4. Synthesis and Characterization of Biogenic Selenium Nanoparticles with Antimicrobial Properties Made by Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. [C] . David Medina, Thomas J. Webster Society for Biomaterials annual meeting and exposition . 2018

机译：金黄色葡萄球菌，耐甲氧西林金黄色葡萄球菌（MRSA），大肠杆菌和铜绿假单胞菌制成的具有抗菌特性的生物硒纳米粒子的合成与表征。
5. Computer-Aided Identification of New DNA Gyrase Inhibitors with Activity against Staphylococcus aureus. [D] . Werner, Malela Mwamufiya. 2014

机译：具有金黄色葡萄球菌活性的新型DNA促旋酶抑制剂的计算机辅助鉴定。
6. Sigma-B a putative operon encoding alternate sigma factor of Staphylococcus aureus RNA polymerase: molecular cloning and DNA sequencing. [O] . S Wu, H de Lencastre, A Tomasz 1996

机译：Sigma-B一个假定的操纵子编码金黄色葡萄球菌RNA聚合酶的另一个σ因子：分子克隆和DNA测序。
7. Sigma-B, a putative operon encoding alternate sigma factor of Staphylococcus aureus RNA polymerase: molecular cloning and DNA sequencing. [O] . Wu, S, de Lencastre, H, Tomasz, A 1996

机译：Sigma-B，一个假定的操纵子，编码金黄色葡萄球菌RNA聚合酶的另一个σ因子：分子克隆和DNA测序。
8. Distamycins and Netropsin as Inhibitors of RNA and DNA Polymerases. [R] . Hahn, F. E. 1977

机译：Distamycins和Netropsin作为RNa和DNa聚合酶的抑制剂。

GPI0363 inhibits the interaction of RNA polymerase with DNA in Staphylococcus aureus

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