Enhancing Antibiotics Efficacy by Combination of Kuraridin and Epicatechin Gallate with Antimicrobials against Methicillin-Resistant Staphylococcus aureus

• Published in: Antibiotics (Basel) Vol. 12; no. 1; p. 117
• Main Authors: Chan, Ben Chung-Lap, Barua, Nilakshi, Lau, Clara Bik-San, Leung, Ping-Chung, Fung, Kwok-Pui, Ip, Margaret
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.01.2023; MDPI
• Subjects: Acids; Antibacterial activity; Antibiotic resistance; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Clinical outcomes; Cytokines; Cytotoxicity; Drug dosages; Drug resistance; Epicatechin; epicatechin gallate; Fusidic acid; Gentamicin; gentamicin and fusidic acid resistance; Green tea; IL-1β; Inflammation; Interleukin 6; kuraridin; Laboratories; Leukocytes (mononuclear); Lungs; Methicillin; MRSA; Natural products; Nosocomial infection; Opportunist infection; Peripheral blood mononuclear cells; Pneumonia; Staphylococcus aureus; Staphylococcus infections; Strains (organisms); Toxins; triple therapy; Tumor necrosis factor-α; Vancomycin; gentamicin and fusidic acid resistance; kuraridin; triple therapy; epicatechin gallate; MRSA
• ISSN: 2079-6382; 2079-6382
• DOI: 10.3390/antibiotics12010117

is an opportunistic pathogen and a major cause of nosocomial and community-acquired infections. The alarming rise in Methicillin-resistant (MRSA) infection worldwide and the emergence of vancomycin-resistant MRSA strains have created an urgent need to identify new and alternative treatment options. Triple combinations of antimicrobials with different antimicrobial mechanisms may be a good choice to overcome antimicrobial resistance. In this study, we combine two natural compounds: kuraridin from and epicatechin gallate (ECG) from (Green tea), which could provide the best synergy with antibiotics against a selected panel of laboratory MRSA with known resistant mechanisms and clinical community-associated (CA) and hospital-associated (HA) MRSA as well. The combined use of ECG and kuraridin was efficacious in inhibiting the growth of a panel of tested MRSA strains. The antibacterial activities of gentamicin, fusidic acid and vancomycin could be further enhanced by the addition of ECG and kuraridin. In time-kill study, when vancomycin (0.5 μg/mL) was combined with ECG (2 μg/mL) and kuraridin (2 μg/mL), a very strong bactericidal growth inhibition against 3 tested strains ATCC25923, MRSA ST30 and ST239 was observed from 2 to 24 h. ECG and kuraridin both possess anti-inflammatory activities in bacterial toxin-stimulated peripheral blood mononuclear cells by suppressing the production of inflammatory cytokines (IL-1β, IL-6 and TNFα) and are non-cytotoxic. In a murine pneumonia model infected with ATCC25923, MRSA ST30 or ST239, the combined use of ECG and kuraridin with vancomycin could significantly reduce bacterial counts. The present findings reveal the potential of ECG and kuraridin combination as a non-toxic herbal and antibiotics combination for MRSA treatment with antibacterial and anti-inflammatory activities.