Antibacterial activity and synergistic antibiotic mechanism of trialdehyde phloroglucinol against methicillin‐resistant Staphylococcus aureus

Abstract

The emergence of methicillin‐resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new anti‐S. aureus agents or therapeutic strategies are urgently needed to treat S. aureus infection. The present study investigated the antibacterial activity of 16 phenolic compounds against MRSA, four of which exhibited antibacterial activity. Their antibacterial activities increased in a dose‐dependent manner but showed different responses with the extension of treatment time. Trialdehyde phloroglucinol (TPG) and 2‐nitrophloroglucinol (NPG) maintained stable antibacterial activity; however, that of dichlorophenol and myricetin decreased rapidly over 24 hr of treatment. Checkerboard and time‐kill assays indicated that TPG and NPG exhibited strong synergistic antibacterial activities with penicillin or bacitracin. Microscopic observation and membrane integrity analysis showed that the combination of TPG and penicillin destroyed the MRSA cell membrane, resulting in the leakage of intracellular biomacromolecules, marked changes in surface zeta potential, and the collapse of membrane potential. Moreover, the combination significantly decreased penicillinase activity and penicillin‐binding protein 2a mRNA expression, inhibiting MRSA growth. Taken together, these results demonstrated that the combination of the phloroglucinol derivative TPG and penicillin has significant synergistic anti‐MRSA activity and can serve as a potential therapeutic strategy to treat MRSA infections.

Synergistic antimicrobial effect and mechanism of enterocin Gr17 and cinnamaldehyde against Escherichia coli and Candida albicans

“…The results suggested that ENT + CEO treatment was bene cial to the neutralization of negative charges on the surface of E. coli and C. albicans cells, resulting in a rapid increase of zeta potential compared with single ENT or CEO treatment. Similar synergistic effect has been reported for trialdehyde phloroglucinol combined with penicillin treatment on the zeta potential of Staphylococcus aureus (Shen et al, 2023). These effects could be mainly ascribed to the electrostatic interactions of the positively charged ENT (PI = 8.82) with negative groups such as lipopolysaccharide of the E. coli surface and phosphatidylserine of the C. albicans surface Sun et al, 2022).…”

“…The zeta potential is a measure of the strength of mutual repulsion or attraction between particles, which re ects the charge distribution on the surface of bacteria and fungus (Shen et al, 2023). As shown in Fig.…”

Untargeted metabolomics‐based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential

“…It has been reported that the strain C. freundii carries a multidrug resistance gene along with it, and is responsible for higher risk of hospital mortality 58 . S. aureus causes disease in both animals and humans and is a contaminant of food 59 . S. aureus has resistance to methicillin due to virulence gene present in it 60 .…”

“…58 S. aureus causes disease in both animals and humans and is a contaminant of food. 59 S. aureus has resistance to methicillin due to virulence gene present in it. 60 S. typhimurium causes nosocomial and food poisoning and has strong pathogenicity due to enterotoxin, endotoxin and extracellular enzymes.…”