Inhibitory Effects on Staphylococcus aureus Sortase A by Aesculus sp. Extracts and Their Toxicity Evaluation

Abstract

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 (<i>Aesculus pavia</i>, <i>A. parviflora</i>, <i>Aesculus x carnea</i>, and <i>A. hippocastanum</i>) were used to prepare ethanol- and water-based extracts for assessing their effect on <i>Staphylococcus aureus</i> 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 <i>Daphnia magna</i> using the median lethal concentration (LC₅₀) and against the fibroblast MRHF cell line. The half maximal inhibitory concentration (IC₅₀) values on sortase A, determined after 30 min of incubation, ranged from 82.70 to 304.31 µg/mL, with the <i>A. pavia</i> water extract exhibiting the highest inhibitory effect. The assessment of the <i>A. pavia</i> 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 <i>Daphnia</i> assay. These findings highlight the low toxicity and the potential of this extract as a promising source of future development of bacteria antivirulence solutions.