State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, China.
Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Virulence. 2021 Dec;12(1):1418-1437. doi: 10.1080/21505594.2021.1928395.
The community-associated Methicillin-resistant strain (CA-MRSA) is highly virulent and has become a major focus of public health professionals. Phenol-soluble modulins (PSM) are key factors in its increased virulence. δ-Toxin belongs to PSM family and has copious secretion in many strains. In addition, δ-toxin exists in the culture supernatant as both N-terminus formylated δ-toxin (fδ-toxin) and deformylated δ-toxin (dfδ-toxin) groups. Although δ-toxin has been studied for more than 70 years, its functions remain unclear. We isolated and purified PSMs from the supernatant of MW2, and found fibrils and oligomers aggregates by Size Exclusion Chromatography. After analyzing PSM aggregates and using peptide simulations, we found that the difference in the monomer structure of fδ-toxin and dfδ-toxin might ultimately lead to differences in the aggregation ability: fδ-toxin and dfδ-toxin tend to form fibrils and oligomers respectively. Of note, we found that fδ-toxin fibrils enhanced the stability of biofilms, while dfδ-toxin oligomers promoted their dispersal. Additionally, oligomeric dfδ-toxin combined with PSMα to form a complex with enhanced functionality. Due to the different aggregation capabilities and functions of fδ-toxin and dfδ-toxin, we speculate that they may be involved in the regulation of physiological activities of . Moreover, the dfδ-toxin oligomer not only provides a new form of complex in the study of PSMα, but also has significance as a reference in oligomer research pertaining to some human amyloid diseases.
社区相关性耐甲氧西林金黄色葡萄球菌（CA-MRSA）具有高度的毒力，已成为公共卫生专业人员关注的主要焦点。酚可溶性调节蛋白（PSM）是其增加毒力的关键因素。δ-毒素属于 PSM 家族，在许多 菌株中大量分泌。此外，δ-毒素以 N 端甲酰化 δ-毒素（fδ-毒素）和去甲酰化 δ-毒素（dfδ-毒素）两种形式存在于培养上清液中。尽管 δ-毒素已经研究了 70 多年，但它的功能仍然不清楚。我们从 MW2 的上清液中分离和纯化了 PSM，并通过排阻色谱发现了纤维和低聚物聚集体。在分析 PSM 聚集体并使用肽模拟后，我们发现 fδ-毒素和 dfδ-毒素单体结构的差异可能最终导致聚合能力的差异：fδ-毒素和 dfδ-毒素倾向于分别形成纤维和低聚物。值得注意的是，我们发现 fδ-毒素纤维增强了生物膜的稳定性，而 dfδ-毒素低聚物促进了它们的分散。此外，低聚物 dfδ-毒素与 PSMα 结合形成具有增强功能的复合物。由于 fδ-毒素和 dfδ-毒素具有不同的聚合能力和功能，我们推测它们可能参与了 生理活动的调节。此外，低聚物 dfδ-毒素不仅为 PSMα 的研究提供了一种新的复合物形式，而且作为某些人类淀粉样蛋白疾病的低聚物研究的参考具有重要意义。
