Department of Infectious Diseases and Department of General Medicine, the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China.
Department of Critical Care Medicine and the Key Lab of Endogenous Infection, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, 518052, China.
Curr Microbiol. 2023 Jun 26;80(8):258. doi: 10.1007/s00284-023-03355-4.
Neobavaisoflavone had antimicrobial activities against Gram-positive multidrug-resistant (MDR) bacteria, but the effect of neobavaisoflavone on the virulence and biofilm formation of S. aureus has not been explored. The present study aimed to investigate the possible inhibitory effect of neobavaisoflavone on the biofilm formation and α-toxin activity of S. aureus. Neobavaisoflavone presented strong inhibitory effect on the biofilm formation and α-toxin activity of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains at 25 µM, but did not affect the growth of S. aureus planktonic cells. Genetic mutations were identified in four coding genes, including cell wall metabolism sensor histidine kinase walK, RNA polymerase sigma factor rpoD, tetR family transcriptional regulator, and a hypothetical protein. The mutation of WalK (K570E) protein was identified and verified in all the neobavaisoflavone-induced mutant S. aureus isolates. The ASN501, LYS504, ILE544 and GLY565 of WalK protein act as hydrogen acceptors to form four hydrogen bonds with neobavaisoflavone by molecular docking analysis, and TRY505 of WalK protein contact with neobavaisoflavone to form a pi-H bond. In conclusion, neobavaisoflavone had excellent inhibitory effect on the biofilm formation and α-toxin activity of S. aureus. The WalK protein might be a potential target of neobavaisoflavone against S. aureus.
新巴西紫檀素具有抗革兰氏阳性多重耐药（MDR）细菌的抗菌活性，但新巴西紫檀素对金黄色葡萄球菌毒力和生物膜形成的影响尚未得到探索。本研究旨在探讨新巴西紫檀素对金黄色葡萄球菌生物膜形成和α-毒素活性的可能抑制作用。新巴西紫檀素在 25 μM 时对甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）菌株的生物膜形成和α-毒素活性均表现出强烈的抑制作用，但不影响浮游细胞的生长。在四个编码基因中鉴定出基因突变，包括细胞壁代谢传感器组氨酸激酶 walK、RNA 聚合酶 σ 因子 rpoD、tetR 家族转录调节因子和一个假定蛋白。在所有新巴西紫檀素诱导的突变金黄色葡萄球菌分离株中鉴定并验证了 WalK（K570E）蛋白的突变。WalK 蛋白的 ASN501、LYS504、ILE544 和 GLY565 作为氢键供体，通过分子对接分析与新巴西紫檀素形成四个氢键，而 WalK 蛋白的 TRY505 与新巴西紫檀素接触形成π-H 键。总之，新巴西紫檀素对金黄色葡萄球菌的生物膜形成和α-毒素活性具有极好的抑制作用。WalK 蛋白可能是新巴西紫檀素抗金黄色葡萄球菌的潜在靶标。
