Olaru Octavian Tudorel, Nitulescu George Mihai, Codreanu Andreea Miruna, Calmuc Valentina-Andreea, Venables Luanne, van de Venter Maryna, Gird Cerasela Elena, Duta-Bratu Cosmina-Gabriela, Nitulescu Georgiana
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
REXDAN Research Infrastructure, "Dunarea de Jos" University of Galati, George Cosbuc Street 98, 800385 Galati, Romania.
Plants (Basel). 2024 May 18;13(10):1405. doi: 10.3390/plants13101405.
A promising strategy for combating bacterial infections involves the development of agents that disarm the virulence factors of pathogenic bacteria, thereby reducing their pathogenicity without inducing direct lethality. Sortase A, a crucial enzyme responsible for anchoring virulence factors to the cell surface of several pathogenic bacteria, has emerged as a possible target for antivirulence strategies. A series of hippocastanum species (, , , and ) were used to prepare ethanol- and water-based extracts for assessing their effect on sortase A. The extracts were characterized through HPLC analysis, and their polyphenols content was determined using the Folin-Ciocalteu method. The specific toxicity profile was evaluated in using the median lethal concentration (LC) and against the fibroblast MRHF cell line. The half maximal inhibitory concentration (IC) values on sortase A, determined after 30 min of incubation, ranged from 82.70 to 304.31 µg/mL, with the water extract exhibiting the highest inhibitory effect. The assessment of the water extract on human fibroblasts revealed no significant signs of toxicity, even at a concentration of 500 µg/mL. This reduced toxicity was further validated through the assay. These findings highlight the low toxicity and the potential of this extract as a promising source of future development of bacteria antivirulence solutions.
一种对抗细菌感染的有前景的策略涉及开发能够消除病原菌毒力因子的药物，从而在不直接致死的情况下降低其致病性。分选酶A是一种负责将毒力因子锚定到几种病原菌细胞表面的关键酶，已成为抗毒力策略的一个可能靶点。使用一系列七叶树属物种（、、和）制备乙醇提取物和水提取物，以评估它们对分选酶A的影响。通过高效液相色谱分析对提取物进行表征，并使用福林-酚法测定其多酚含量。使用半数致死浓度（LC）在中评估其特定毒性概况，并针对成纤维细胞MRHF细胞系进行评估。孵育30分钟后测定的对分选酶A的半数最大抑制浓度（IC）值范围为82.70至304.31μg/mL，其中水提取物表现出最高的抑制作用。对人成纤维细胞的水提取物评估显示，即使在浓度为500μg/mL时也没有明显的毒性迹象。通过试验进一步验证了这种降低的毒性。这些发现突出了这种提取物的低毒性以及作为未来细菌抗毒力解决方案有前景的开发来源的潜力。
