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. 2017 Oct 5;7(1):12721.
doi: 10.1038/s41598-017-12905-3.

Chlorinated emodin as a natural antibacterial agent against drug-resistant bacteria through dual influence on bacterial cell membranes and DNA

Feixia Duan  1   2 , Guang Xin  1 , Hai Niu  1   3 , Wen Huang  4
Affiliations

Chlorinated emodin as a natural antibacterial agent against drug-resistant bacteria through dual influence on bacterial cell membranes and DNA

Feixia Duan et al. Sci Rep. .

Abstract

The rise in infections caused by drug-resistant pathogens and a lack of effective medicines requires the discovery of new antibacterial agents. Naturally chlorinated emodin 1,3,8-trihydroxy-4-chloro-6-methyl-anthraquinone (CE) from fungi and lichens was found to markedly inhibit the growth of Gram-positive bacteria, especially common drug-resistant bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). CE was confirmed to cause significant potassium leakage, cell membrane depolarization and damage to the selective permeability of cell membranes in bacterial cells, resulting in bacterial cell death. In addition, CE was shown to have a strong electrostatic interaction with bacterial DNA and induce DNA condensation. Thus, CE is a promising natural antibacterial pharmacophore against Gram-positive bacteria, especially common drug-resistant MRSA and VRE isolates, with a dual antibacterial mechanism that damages bacterial cell membranes and DNA.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
The chemical structures of CE and emodin. (a) CE; (b) emodin.
Figure 2
Figure 2
The growth of E. coli ATCC 25922 treated with gradual concentrations of CE in the presence of PMBN. The growth of E. coli ATCC 25922 was represented by the difference in the ODi and ODu values, where ODi and ODu are the optical density of inoculated medium and the corresponding uninoculated well. Plots show means of triplicates with SD.
Figure 3
Figure 3
The potassium leakage and transmembrane potential of the bacterial cells treated with CE and emodin. (a,b) The K+ concentrations in the supernatants of S. aureus (a) and B. cereus (b) cell suspensions treated with 16 μg/ml of CE and emodin; plots show means of triplicates with SD. (c) T The fluorescence intensity of Rh123 stained S. aureus and B. cereus cells treated with 16 μg/ml of CE for 1 h; heights show mean values of triplicates with SD. Controls (without treatment with CE or emodin) are also shown in each panel.
Figure 4
Figure 4
The micrograph of PI/DAPI dual-stained bacterial cells treated with CE observed with inverted fluorescence microscope. (a) B. cereus cells. (b) S. aureus cells. Samples without treatment of CE were set as control. In each panel, controls were shown in (i) (ii) and (iii), and the cells treated with 4 μg/ml of CE for 20 min in (iv) (v) and (vi); the bacterial cells observed under white light are shown in (i) and (iv); samples excited by blue light are shown in (ii) and (v), and that excited by green light in (iii) and (vi).
Figure 5
Figure 5
The CE-induced fluorescence quenching of DNA-PI and DNA-DAPI complexes. (a) The fluorescence intensity detected in the DAPI-stained S. aureus and B. cereus cells treated with 16 μg/ml of CE; the wave-length of exciting light was 358 nm; samples without treatment of CE are shown as Control. (b) The fluorescence spectra of DNA-DAPI complex in Tris-HCl buffer (10 mM, pH 7.2) with increasing concentrations of CE; 1–6 means: the concentrations of CE at 0, 10, 20, 40, 80 and 160 μM. (c,d) The fluorescence spectra of DNA-PI complex in Tris-HCl buffer (10 mM, pH 7.2) with increasing concentrations of CE (c) and emodin (d); 1–5 means: the concentrations of CE at 0, 20, 40, 60 and 80 μM; 1′-5′ means: the concentrations of emodin at 0, 20, 40, 60 and 80 μM. (e) The calculation of K SV value in CE-induced fluorescence quenching of DNA-PI complex at 298 K and 308 K. (f) The calculation of the reaction constant (K a) and the binding site (n) of CE with the DNA-PI complex. Micrococcus luteus genomic DNA was used in the experiment.
Figure 6
Figure 6
The UV-Vis spectra and CD spectra of the solution containing of CE and Micrococcus luteus genomic DNA. (a) The UV-Vis spectra of the solution containing of CE (20 μM) and increasing concentrations of DNA in Tris-HCl buffer (10 mM, pH 7.2); 1–5 means: the concentrations of DNA at 0, 5, 10, 15, 20 and 25 μM. (b) The sum of the individual absorbance of the CE (20 μM) and DNA (15 μM) in Tris-HCl buffer (10 mM, pH 7.2) and the individual absorbance of CE and DNA. (c) The CD spectra of DNA (0.01 mM) in Tris-HCl buffer (10 mM, pH 7.2)with increasing concentrations of CE; 1–3 means: the concentrations of CE at 0, 20 and 40 μM.
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