Biofilm-associated Agr and Sar quorum sensing systems of staphylococcus aureus are inhibited by 3-hydroxybenzoic acid derived from illicium verum

Ganesh, Pitchaipillai Sankar and Veena, Krishnamurthy and Senthil, Renganathan and Iswamy, Koneti and Ponmalar, Esaki Muthu and Mariappan, Vanitha and Girija, A. S. Smiline and Vadivelu, Jamuna and Nagarajan, Samuthira and Challabathula, Dinakar and Shankar, Esaki Muthu (2022) Biofilm-associated Agr and Sar quorum sensing systems of staphylococcus aureus are inhibited by 3-hydroxybenzoic acid derived from illicium verum. ACS Omega, 7 (17). pp. 14653-14665. ISSN 2470-1343, DOI https://doi.org/10.1021/acsomega.1c07178.

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Abstract

Biofilm-producing Staphylococcus aureus (S. aureus) is less sensitive to conventional antibiotics than free-living planktonic cells. Here, we evaluated the antibiofilm activity of Illicium verum (I. verum) and one of its constituent compounds 3-hydroxybenzoic acid (3-HBA) against multi-drug-resistant S. aureus. We performed gas chromatography-mass spectroscopy (GC-MS) to identify the major constituents in the methanolic extract of I. verum. Ligand-receptor interactions were studied by molecular docking, and in vitro investigations were performed using crystal violet assay, spreading assay, hemolysis, proteolytic activity, and growth curve analysis. The methanolic extract of I. verum inhibited S. aureus at 4.8 mg/mL, and GC-MS analysis revealed anethole, m-methoxybenzaldehyde, and 3-HBA as the major constituents. Molecular docking attributed the antibiofilm activity to an active ligand present in 3-KBA, which strongly interacted with the active site residues of AgrA and SarA of S. aureus. At a subinhibitory concentration of 2.4 mg/mL, the extract showed biofilm inhibition. Similarly, 3-HBA inhibited biofilm activity at 25 mu g/mL (90.34%), 12.5 mu g/mL (77.21%), and 6.25 mu g/mL (62.69%) concentrations. Marked attrition in bacterial spreading was observed at 2.4 mg/mL (crude extract) and 25 mu g/mL (3-HBA) concentrations. The methanol extract of I. verum and 3-HBA markedly inhibited beta-hemolytic and proteolytic activities of S. aureus. At the lowest concentration, the I. verum extract (2.4 mg/mL) and 3-HBA (25 mu g/mL) did not inhibit bacterial growth. Optical microscopy and SEM analysis confirmed that I. verum and 3-HBA significantly reduced biofilm dispersion without disturbing bacterial growth. Together, we found that the antibiofilm activity of I. verum and 3-KBA strongly targeted the Agr and Sar systems of S. aureus.

Item Type: Article
Funders: None
Uncontrolled Keywords: Particle Mesh Ewald; Anti-biofilm; Antibiotic-resistance; Tannic-acid; In-vitro; Protein; Mrsa; Identification; Pathogenesis; Infection
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine > School of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 19 Oct 2023 03:28
Last Modified: 19 Oct 2023 03:28
URI: http://eprints.um.edu.my/id/eprint/41995

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