title: The promiscuous and synergic molecular interaction of polyphenols in bactericidal activity: an opportunity to improve the performance of antibiotics?
abstract: Plant polyphenols are a potential source of new antimicrobial molecules against bacteria because most newly developed antimicrobial agents do not improve the clinical management of infectious diseases. The potential synergism between the major polyphenolic compounds present in a Cistus salviifolius extract, which was characterized by HPLC-ESI-MS/MS, was investigated by the isobole method and the fractional inhibitory concentration index determination. Pairwise combinations of selected flavonoids and ellagitannins present in C. salviifolius extract were assayed against the in vitro growth of Staphylococcus aureus. Some combinations revealed synergic effects, resulting in a reduction of the minimum inhibitory concentration required to inhibit 50% growth (MIC50 ) up to 20 times lower as compared with the individual compounds. Some of the combinations exhibited MIC50 values close to drug potency level (0.5-1 µg/mL). Punicalagin and myricetin were the major contributors in the combinations. The proportion between the compounds in the synergic mixtures is crucial and may explain the superior antimicrobial activity displayed by this extract when compared with other botanical extracts. The rational optimization of these combinations could lead to the design of potent antimicrobial phytopharmaceuticals, which may improve the performance of current antibiotics, taking advantage of the multi-targeted and synergic molecular interactions of selected polyphenols.
authors.affiliation: Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández, Avenida de la Universidad s/n. E-03202 Elche, Alicante, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Tomás-Menor
authors.forename: Enrique
authors.initials: E
authors.lastname: Barrajón-Catalán
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.forename: Nuria
authors.initials: N
authors.lastname: Martí
authors.forename: Domingo
authors.initials: D
authors.lastname: Saura
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menéndez
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Vicente
authors.initials: V
authors.lastname: Micol
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000904:Antibiotics, Antitubercular / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D029758:Cistus / Q000737:chemistry*; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D005419:Flavonoids; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D059808:Polyphenols; C115642:punicalagin; C040015:myricetin
keywords: Cistus; Staphylococcus; ellagitannins; flavonols; punicalagin; synergy