1Department of Infectious Diseases and Shenzhen Key Laboratory for Endogenous Infections, Shenzhen Nanshan People's Hospital, and the 6th Affiliated Hospital of Shenzhen University Medical School, Shenzhen, China.
2Department 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, China.
Pol J Microbiol. 2023 Jun 14;72(2):199-208. doi: 10.33073/pjm-2023-021. eCollection 2023 Jun 1.
Alpha-mangostin (α-mangostin) was discovered as a potent natural product against Gram-positive bacteria, whereas the underlying molecular mechanisms are still unclear. This study indicated that α-mangostin (at 4 × MIC) rapidly killed planktonic cells more effectively (at least 2-log CFU/ml) than daptomycin, vancomycin and linezolid at 1 and 3 h in the time-killing test. Interestingly, this study also found that a high concentration of α-mangostin (≥4×MIC) significantly reduced established biofilms of . There were 58 single nucleotide polymorphisms (SNPs) in α-mangostin nonsensitive isolates by whole-genome sequencing, of which 35 SNPs were located on both sides of the gene and 10 SNPs in the gene. A total of 147 proteins with a different abundance were determined by proteomics analysis, of which 91 proteins increased, whereas 56 proteins decreased. The abundance of regulatory proteins SarX and SarZ increased. In contrast, the abundance of SarT and IcaB was significantly reduced (they belonged to SarA family and system, associated with the biofilm formation of ). The abundance of cell membrane proteins VraF and DltC was augmented, but the abundance of cell membrane protein UgtP remarkably decreased. Propidium iodide and DiBaC(3) staining assay revealed that the fluorescence intensities of DNA and the cell membrane were elevated in the α-mangostin treated isolates. In conclusion, this study reveals that α-mangostin was effective against planktonic cells by targeting cell membranes. The anti-biofilm effect of α-mangostin may be through inhibiting the function of SarT and IcaB.
α-倒捻子素（α-mangostin）被发现是一种对抗革兰氏阳性菌的有效天然产物，但其潜在的分子机制尚不清楚。本研究表明，α-倒捻子素（在 4×MIC 时）在杀伤试验中，在 1 和 3 小时时比达托霉素、万古霉素和利奈唑胺更有效地快速杀死浮游细胞（至少 2-log CFU/ml）。有趣的是，本研究还发现高浓度的α-倒捻子素（≥4×MIC）显著减少了 生物膜的形成。通过全基因组测序，在对α-倒捻子素不敏感的 分离株中发现了 58 个单核苷酸多态性（SNP），其中 35 个 SNP 位于 基因的两侧，10 个 SNP 位于 基因内。通过蛋白质组学分析确定了 147 种具有不同丰度的蛋白质，其中 91 种蛋白质增加，而 56 种蛋白质减少。调节蛋白 SarX 和 SarZ 的丰度增加。相比之下，SarT 和 IcaB 的丰度显著降低（它们属于 SarA 家族和 系统，与 的生物膜形成有关）。细胞膜蛋白 VraF 和 DltC 的丰度增加，而细胞膜蛋白 UgtP 的丰度显著降低。碘化丙啶和 DiBaC（3）染色实验表明，α-倒捻子素处理的 分离株中 DNA 和细胞膜的荧光强度增加。总之，本研究表明，α-倒捻子素通过靶向细胞膜对浮游细胞有效。α-倒捻子素的抗生物膜作用可能是通过抑制 SarT 和 IcaB 的功能来实现的。
