Exploring the antimicrobial effects of synthetic gallotannins on Gram-negative bacteria, and pathogenic and food-spoilage yeasts

Background Gallotannins (GTs) are polyphenolic compounds with reported antimicrobial properties, but the relationship between their molecular structure and their activity against Gram-negative bacteria and yeasts remains insufficiently understood. Synthetic analogues of natural GTs provide structurally-defined molecules for the investigation of structure-activity relationships and the identification of compounds with improved or complementary properties. Methods The antibacterial activity of synthetic structural analogues of the natural 1,2,3,4,6-penta- O -galloyl-D-glucose (PGG) and hamamelitannin (HT) was evaluated against Escherichia coli and Pseudomonas aeruginosa , by assessing bacterial growth, cell-surface hydrophobicity, membrane permeability, and biofilm-associated biomass. Their effects in combination with ciprofloxacin or polymyxin B sulphate were also investigated. The antifungal activity was evaluated against a panel of five pathogenic Candida -related yeasts and ten food-spoilage yeast species. Results The differences between the GTs, in terms of efficacy, depended on their chemical structure. PGG and the HT analogue, 2’,5-di- O -galloyl-2- C -(hydroxymethyl)-2,3- O- isopropylidene- d -lyxose (G 2 Lyx), showed the greatest inhibition of E. coli growth, whereas methyl 2,3,4-tri- O -galloyl-α-L-rhamnoside (G 3 Rham) was most active against P. aeruginosa , reducing the growth response by approximately 50% at 8 µg/mL. GTs also altered, to various extents, the bacterial surface hydrophobicity and membrane permeability, depending on the compound and the strain. They did not significantly reduce the biofilm-associated biomass, whereas several analogues, in combination with ciprofloxacin or polymyxin B sulphate, reduced the biomass of P. aeruginosa . PGG and its analogues, methyl 2,3,4,6-tetra- O -galloyl-α-D-glucoside (G 4 Glc), methyl 2,3,4,6-tetra- O -galloyl-α-D-mannoside (G 4 Man), and methyl 2,3,4-tri- O -galloyl-α-L-rhamnoside (G 3 Rham), were most effective against yeasts. Conclusions Synthetic GTs demonstrated distinct, structure- and microorganism-dependent growth-inhibitory effects against Gram-negative bacteria and yeasts. G 3 Rham showed the most pronounced effect against P. aeruginosa , while PGG, G 4 Glc, and G 4 Man were particularly active against several yeast species. The observed changes in bacterial surface properties and the ability to modulate biofilm-associated biomass, in combination with antibiotics, suggest that these compounds may influence microbial responses through multiple mechanisms.