| Autor: |
Mizar, Pushpak, Arya, Rekha, Kim, Truc, Cha, Soyoung, Ryu, Kyoung-Seok, Yeo, Won-Sik, Bae, Taeok, Kim, Dae Wook, Park, Ki Hun, Kim, Kyeong Kyu, Lee, Seung Seo |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Popis: |
As an alternative strategy to fight antibiotic resistance, two-component systems (TCSs) have emerged as novel targets. Among TCSs, master virulence regulators that control the expression of multiple virulence factors are considered as excellent anti-virulence targets. In Staphylococcus aureus, virulence factor expression is tightly regulated by a few master regulators, including the SaeRS TCS. In this study, we used a SaeRS GFP-reporter system to screen natural compound inhibitors of SaeRS, and identified xanthoangelol B 1, a prenylated chalcone from Angelica keiskei as a hit. We have synthesized 1 and its derivative PM-56, and shown that 1 and PM-56 both had excellent inhibitory potency against the SaeRS TCS, as demonstrated by various in vitro and in vivo experiments. As a mode of action, 1 and PM-56 were shown to bind directly to SaeS and inhibit its histidine kinase activity, which suggests a possibility of a broad spectrum inhibitor of histidine kinases. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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