The Effect of Calcium and Halide Ions on the Gramicidin A Molecular State and Antimicrobial Activity

Abstract

Gramicidin A (gA) forms several convertible conformations in different environments. In this study, we investigated the effect of calcium halides on the molecular state and antimicrobial activity of gramicidin A. The molecular state of gramicidin A is highly affected by the concentration of calcium salt and the type of halide anion. Gramicidin A can exist in two states that can be characterized by circular dichroism (CD), mass, nuclear magnetic resonance (NMR) and fluorescence spectroscopy. In State 1, the main molecular state of gramicidin A is as a dimer, and the addition of calcium salt can convert a mixture of four species into a single species, which is possibly a left-handed parallel double helix. In State 2, the addition of calcium halides drives gramicidin A dissociation and denaturation from a structured dimer into a rapid equilibrium of structured/unstructured monomer. We found that the abilities of dissociation and denaturation were highly dependent on the type of halide anion. The dissociation ability of calcium halides may play a vital role in the antimicrobial activity, as the structured monomeric form had the highest antimicrobial activity. Herein, our study demonstrated that the molecular state was correlated with the antimicrobial activity.

Effects of Calcium Ions on the Antimicrobial Activity of Gramicidin A

“…Both the hydroxyl free radical formation and dysregulation of the NAD + /NADH mechanism have been linked with the antimicrobial activity of gramicidin A [ 18 ]. Also, the antimicrobial activity of gramicidin A is highly associated with the conformation of gramicidin A [ 19 , 20 , 21 ]. Several studies have demonstrated that gramicidin A, only in a channel form, is able to proceed with its antimicrobial activity [ 19 , 20 , 21 ].…”

“…Also, the antimicrobial activity of gramicidin A is highly associated with the conformation of gramicidin A [ 19 , 20 , 21 ]. Several studies have demonstrated that gramicidin A, only in a channel form, is able to proceed with its antimicrobial activity [ 19 , 20 , 21 ]. Ca 2+ ions have been found to block the translocation of alkali cations of gA across membrane lipids and convert gA double helical dimers into helical monomers [ 21 , 22 , 23 ].…”

“…Several studies have demonstrated that gramicidin A, only in a channel form, is able to proceed with its antimicrobial activity [ 19 , 20 , 21 ]. Ca 2+ ions have been found to block the translocation of alkali cations of gA across membrane lipids and convert gA double helical dimers into helical monomers [ 21 , 22 , 23 ]. However, the effect of Ca 2+ ions on the antimicrobial activity of gramicidin A remains unresolved.…”

“…Arndt and his co-worker demonstrated that only the gramicidin A analogs with tail-to-tail antiparallel single strand β 6.3 -helix mediated antimicrobial and antimalarial activities [ 19 ]. In a recent study, we showed that calcium ions could dissociate double helix into single-strand helical monomer [ 21 ]. In this study, we further demonstrated that the single-strand helical monomer has the highest antimicrobial activity compared to the double helical dimer [ 21 ].…”

“…In a recent study, we showed that calcium ions could dissociate double helix into single-strand helical monomer [ 21 ]. In this study, we further demonstrated that the single-strand helical monomer has the highest antimicrobial activity compared to the double helical dimer [ 21 ]. All these studies indicated that the gramicidin channel, instead of the gramicidin double helical dimer, is likely to be the active antimicrobial form.…”