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

Author:

Olaru Octavian Tudorel1ORCID,Nitulescu George Mihai1ORCID,Codreanu Andreea Miruna2,Calmuc Valentina-Andreea2,Venables Luanne3,van de Venter Maryna3ORCID,Gird Cerasela Elena1ORCID,Duta-Bratu Cosmina-Gabriela1,Nitulescu Georgiana1ORCID

Affiliation:

1. Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania

2. REXDAN Research Infrastructure, “Dunarea de Jos” University of Galati, George Cosbuc Street 98, 800385 Galati, Romania

3. Department of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South Africa

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 (Aesculus pavia, A. parviflora, Aesculus x carnea, and A. hippocastanum) were used to prepare ethanol- and water-based extracts for assessing their effect on Staphylococcus aureus 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 Daphnia magna 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 A. pavia water extract exhibiting the highest inhibitory effect. The assessment of the A. pavia 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 Daphnia assay. These findings highlight the low toxicity and the potential of this extract as a promising source of future development of bacteria antivirulence solutions.

Publisher

MDPI AG

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