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Paper 26 November 2024

Antimicrobial Activity of Glycyrrhizinic Acid is pH-Dependent

In recent years, antimicrobial hydrogels have attracted much attention in biomedical applications due to their biocompatibility and high water content. Glycyrrhizin (GA) is an antimicrobial that can form pH-dependent hydrogels due to the three carboxyl groups of GA that differ in pKa value. The influence of GA protonation on the antimicrobial activity, however, has never been studied before. Therefore, we investigated the effect of the pH on the antimicrobial activity of GA against various bacteria, including ESKAPE pathogens. This activity cannot solely be attributed to the resulting pH decrease of the suspension, as the presence of GA significantly increases the activity. Instead, this increased activity is due to the release of GA from the hydrogel into the suspension, where it directly interacts with the bacteria. Moreover, we provide evidence indicating that the pH dependency of the antimicrobial activity is due to differences in GA protonation state by treating the pathogens with GA solutions differing in their GA protonation distribution. Overall, our results demonstrate that the pH influences not only the physical but also the antimicrobial properties of the GA hydrogels.