The direct anti-MRSA effect of emodin via damaging cell membrane

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has become an important bacterium for nosocomial infection. Only a few antibiotics can be effective against MRSA. Therefore, searching for new drugs against MRSA is important. Herein, anti-MRSA activities of emodin and its mechanisms were investigated. Firstly, in vitro antimicrobial activity was investigated by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-growth curve, and multipassage resistance testing was performed. Secondly, protection of emodin on mice survival and blood bacterial load in mice challenged with lethal or sublethal dose of MRSA were investigated. Subsequently, the influences of emodin on the bacterial morphology, messenger RNA (mRNA) expressions related to cell wall synthesis and lysis, β-lactamase activity, drug accumulation, membrane fluidity, and integrity were performed to investigate its mechanisms. Lastly, in vitro cytotoxicity assay were performed using the 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) method. The results showed MICs and MBCs of emodin against MRSA252 and 36 clinical MRSA strains were among 2-8 and 4-32 μg/mL, respectively. There was no MIC increase for emodin during 20 passages. In vivo, emodin dose-dependently protected mice challenged with lethal dose of MRSA and decreased bacterial load in mice challenged with sublethal dose of MRSA. Morphology observation showed emodin might disrupt cell wall and membrane of MRSA. Although emodin had no influence on genes related to cell wall synthesis and lysis as well as β-lactamase activity and drug accumulation, emodin reduced membrane fluidity and disrupted membrane integrity. Based on the fact that emodin had no significant cytotoxicity against mammalian cells, it could be further investigated as a membrane-damage bactericide against MRSA in the future.

Self-assembled natural phytochemicals for synergistically antibacterial application from the enlightenment of traditional Chinese medicine combination

“…It is reported that the cytoderm of gram-positive bacteria is the main acting site of emodin 41 , 42 , 43 . Analysis showed that anthraquinone ring had strong affinity to membrane.…”

Root tuber extract of <i>Polygooum cillinerve</i> (Nakai) Ohwi exerts antimicrobial and immunomodulatory activities

“…Consistent with the records of Bencao Tujing (published in 1061, China), rPC served as an anti-infection agent. Emodin and physcion, the effective of rPC, have strong bactericidal effects [5,13,14]. Therefore, rPC possessed natural antibacterial activity.…”

Emodin Successfully Inhibited Invasion of Brucella abortus Via Modulting Adherence, Microtubule Dynamics and ERK Signaling Pathway in RAW 264.7 Cells

“…The antibacterial efficacy of emodin has been demonstrated against several microorganisms including Bacillus subtilis, Staphylococcus aureus, Helicobacter pylori and Haemophilus parasuis [17][18][19][20]. It has been observed that the antibacterial activity of emodin was concentration-dependent and attributed to its ability to destroy cell membrane integrity, increase membrane permeability and DNA damage [20].…”