Calycosin enhances the bactericidal efficacy of polymyxin B by inhibiting MCR‐1 in vitro

Abstract

Aim: To examine the synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains. Methods and Results: In this study, we found a potential inhibitor of MCR-1, calycosin, that could significantly restore the antibacterial activity of polymyxin B. The synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains was confirmed by checkerboard minimum inhibitory concentration assays, time-kill curve assays and disk diffusion assays. The fractional inhibitory concentration indexes ranged from 0Á15 AE 0Á03 to 0Á28 AE 0Á05, and the zones of inhibition increased from 13Á33 AE 0Á47 to 17Á67 AE 0Á47 mm with the combined therapy of calycosin and polymyxin B. In addition, the combined therapy significantly reduced the number of bacteria in the medium. However, at the concentrations required for the synergistic effect with polymyxin B, calycosin alone showed no effect on bacterial growth or MCR-1 production. Calycosin treatment exhibited no cytotoxicity to HeLa cells or A549 cells at calycosin concentrations below 32 µg ml À1. Conclusions: Therefore, our results suggested that calycosin could be used as a potential MCR-1 inhibitor to restore the bactericidal effect of polymyxin B without affecting bacterial viability or existing cytotoxicity. Significance and Impact of the Study: The synergistic effect of calycosin combined with polymyxin B against various mcr-1-positive bacterial strains paves the way for future pharmaceutical applications of calycosin in fighting mcr-1-positive bacterial infections.

Global epidemiology, genetic environment, risk factors and therapeutic prospects of mcr genes: A current and emerging update

“…Natural/organic compounds identified with a synergistic effect on colistin include Honokiol (Guo et al, 2020), Isoalantolactone (IAL) (Lu et al, 2020), Calycosin (Liu et al, 2020) and Eugenol . Honokiol was derived from the dry skin and bark of Magnolia officinalis (Guo et al, 2020), IAL is the main sesquiterpene lactone from Radix inulae and other plants (Lu et al, 2020).…”

Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

“…Natural/organic compounds identified with a synergistic effect on colistin include Honokiol 186 , Isoalantolactone (IAL) 187 , Calycosin 188 and Eugenol 189 . Honokiol was derived from the dry skin and bark of Magnolia officinalis 186 , IAL is the main sesquiterpene lactone from Radix inulae and other plants 187 , Calycosin is a flavonoid from a direct root extract of the traditional Chinese medicinal herb, Radix astragali.…”

“…Honokiol was derived from the dry skin and bark of Magnolia officinalis 186 , IAL is the main sesquiterpene lactone from Radix inulae and other plants 187 , Calycosin is a flavonoid from a direct root extract of the traditional Chinese medicinal herb, Radix astragali. 188 Lastly, Eugenol is a phenylpropanoid, an essential oil isolated from plants 190 . Each of these compounds, when combined with colistin, decreased colistin MICs and increased colistin’s bactericidal activity against colistin-resistant isolates.…”

“…(2020) 186 and Liu et al . (2020) 188 showed that the natural compounds, honokiol and calycosin, in combinations with colistin, respectively reduced the load of bacteria and improved viability in animal models.…”

Calycosin may Alleviate Ang II-Induced Pro-proliferative Effects on Glomerular Mesangial Cells <i>via</i> Partially Inhibiting Autophagy and ERK Signaling Pathway

“…With the development of medical science and pharmaceutical science, the therapeutic functions of extractives that derived from the natural plants 11,12) have been investigated in many previous studies. Calycosin is the active component of traditional Chinese medicine Astragali Radix, and as many other natural extractives, it can be widely found and isolated from many kinds of plants, vegetables, and fruits [13][14][15] . Calycosin have exerted anti-oxidant, anti-fibrotic, anti-bacterial as well as anti-inflammatory activities 16,17) .…”