Flavonolignans from silymarin modulate antibiotic resistance and virulence in Staphylococcus aureus

0557462 - MBÚ 2023 RIV FR eng J - Journal Article
Holasová, K. - Křížkovská, B. - Hoang, L. - Dobiasová, S. - Lipov, J. - Macek, T. - Křen, Vladimír - Valentová, Kateřina - Ruml, T. - Viktorová, J.
Flavonolignans from silymarin modulate antibiotic resistance and virulence in Staphylococcus aureus.
Biomedicine & Pharmacotherapy. Roč. 149, May 2022 (2022), č. článku 112806. ISSN 0753-3322. E-ISSN 1950-6007
R&D Projects: GA MŠMT(CZ) LTC20070; GA ČR GA21-00551S
Institutional support: RVO:61388971
Keywords : nora efflux pump * multidrug-resistance * ampicillin-sulbactam * biofilm formation * pcr assay * silibinin * expression * vitro * antibacterial * derivatives * Flavonolignans * Silybin * Silychristin * Multidrug resistance * Staphylococcus aureus * Efflux pump
OECD category: Pharmacology and pharmacy
Impact factor: 7.5, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0753332222001949?via%3Dihub

Antibiotic resistance is currently a serious health problem. Since the discovery of new antibiotics no longer seems to be a sufficient tool in the fight against multidrug-resistant infections, adjuvant (combination) therapy is gaining in importance as well as reducing bacterial virulence. Silymarin is a complex of flavonoids and fla-vonolignans known for its broad spectrum of biological activities, including its ability to modulate drug resis-tance in cancer. This work aimed to test eleven, optically pure silymarin flavonolignans for their ability to reverse the multidrug resistance phenotype of Staphylococcus aureus and reduce its virulence. Silybin A, 2,3-dehydrosi-lybin B, and 2,3-dehydrosilybin AB completely reversed antibiotic resistance at concentrations of 20 mu M or less. Both 2,3-dehydrosilybin B and AB decreased the antibiotic-induced gene expression of representative efflux pumps belonging to the major facilitator (MFS), multidrug and toxic compound extrusion (MATE), and ATP-binding cassette (ABC) families. 2,3-Dehydrosilybin B also inhibited ethidium bromide accumulation and efflux in a clinical isolate whose NorA and MdeA overproduction was induced by antibiotics. Most of the tested flavonolignans reduced cell-to-cell communication on a tetrahydrofuran-borate (autoinducer-2) basis, with isosilychristin leading the way followed by 2,3-dehydrosilybin A and AB, which halved communication at 10 mu M. Anhydrosilychristin was the only compound that reduced communication based on acyl-homoserine lactone (autoinducer 1), with an IC50 of 4.8 mu M. Except for isosilychristin and anhydrosilychristin, all of the fla-vonolignans inhibited S. aureus surface colonization, with 2,3-dehydrosilybin A being the most active (IC50 10.6 mu M).
Permanent Link: http://hdl.handle.net/11104/0331460