Co-interaction of nitrofurantoin and saponins surfactants with biomembrane leads to an increase in antibiotic’s antibacterial activity

Abstract

Limited bioavailability of antibiotics is an urgent problem in the treatment of microbial infections. To increase transport of nitrofurantoin (NFT) into the bacterial cells the proposed strategy is to use the natural surfactants - saponins, extracted from Sapindus mukorossi L. This study aimed to investigate whether and in which way saponins may increase the antibacterial action of nitrofurantoin against Gram-negative bacteria Pseudomonas aeruginosa NFT3 strain. The results clearly show that the cell activity of bacteria treated with NFT was nearly 35% lower after 8 h, but in the presence of S. mukorossi L. saponins over 75% reduction in the activity of the cells was observed. The Langmuir monolayer technique proved the incorporation of plant surfactant molecules into the phospholipid membrane and the lack of membrane interaction of NFT itself. The analysis with live bacterial cells showed a significant decrease in total cell membrane permeability, which was observed in the presence of NFT (reduction from 16% to 7%) with a negligible effect of saponins alone on this parameter. TEM and AFM imaging confirmed the deformation of the bacterial cell wall in the presence of saponins. To conclude, the synergistic co-action of the S. mukorossi L. saponins and NFT was proved, and it could be explained by membrane relaxation caused by saponins, which facilitates the bioavailability of NFT on the bacteria and increases its effectiveness as a biocidal agent. The research results indicate the possibility of using new, biodegradable surfactants, i.e. saponins, in antibiotic therapies.