Glycyrrhizic Acid Decreases Gentamicin-Resistance in Vancomycin-Resistant Enterococci

Abstract

The resistance of commensal bacteria against first and second line antibiotics has reached an alarming level in many parts of the world and endangers the effective treatment of infectious diseases. Particularly vancomycin-resistant represents an increasing clinical problem in the treatment of infectious diseases and hinders adequate antibiotic stewardship. In consideration of the lack of novel antibiotic compounds, the development of resistance-modifying agents, however, can mitigate the spread of bacterial drug resistance and might possibly extend the useful application indices of an existing licensed antibiotic. Given that saponins modify the local chemical environment at cell membranes and might modify the uptake or mode of action of antibiotics in bacteria, we investigated the influence of the triterpenoid saponin glycyrrhizic acid of on the susceptibility of vancomycin-resistant enterococci against the aminoglycoside antibiotic gentamicin in 47 clinical isolates by applying the checkerboard method. The fractional inhibitory concentration indices values were determined between 0.016 and ≤ 0.5 (synergy is accepted with values ≤ 0.5). Glycyrrhizic acid at the subinhibitory concentration of 2.4 mM was found to reduce the minimal inhibitory concentration of gentamicin in intrinsically resistant strains down to 6.25 % of the minimal inhibitory concentration of gentamicin alone, whereas relatively low concentrations of glycyrrhizic acid (18 µM) resulted in increased susceptibilities for some isolates to gentamicin. In conclusion, our study points towards a therapeutic potential of glycyrrhizic acid in co-application with gentamicin for defined local bacterial infections caused by vancomycin resistant strains.

Novel Opportunity to Reverse Antibiotic Resistance: To Explore Traditional Chinese Medicine With Potential Activity Against Antibiotics-Resistance Bacteria

“…Piperine isolated from black pepper was shown to enhance antimicrobial activity of mupirocin against S. aureus strains including MASA through the inhibition of efflux of ethidium bromide (Mirza et al, 2011). In addition, Schmidt et al (2016) revealed therapeutic potential of glycyrrhizic acid in coapplication with gentamicin for defined local bacterial infections caused by vancomycin-resistant Enterococcus strains, indicating that glycyrrhizic acid improve the antimicrobial activity of gentamicin to antibiotic-resistant bacteria ( Table 1).…”

Synergistic antimicrobial effects of Cefabronchin®

“…Multi-drug therapy is less vulnerable to adaptive resistance due to biological systems being less able to compensate effects from two or more substances or from one substance that acts on multiple targets simultaneously [33]. A shift in the way chemotherapy has been approached in the last few years indicates that multidrug therapies are going to replace mono-substance therapies in the near future as the standing paradigm [34].…”

Traditional Uses, Pharmacological Effects, and Molecular Mechanisms of Licorice in Potential Therapy of COVID-19

“…Much of researches in antibacterial effect have found that licorice can exert antibacterial effects by inhibiting pathogenic bacteria and reducing the bacterial gene expression. For instance, 2.4 mM glycyrrhizin decreased the minimum inhibitory concentration (MIC) of gentamicin from >8 mg/L to ≤0.125 mg/L (Schmidt et al, 2016). Long investigated the antibacterial effect of glycyrrhizin on methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model of skin infection.…”