Pithecellobium clypeariaextract enriched in gallic acid and luteolin has antibacterial activity against MRSA and reduces resistance to erythromycin, ceftriaxone sodium and levofloxacin

Abstract
Aims Antibiotic adjuvants can give a second life to the antibiotics to which bacteria are highly resistant. We evaluated the antimicrobial effects of extracts from Pithecellobium clypearia against MRSA and also the potential for synergy with several antibiotics. Methods and Result For this study, four extracts from P. clypearia were tested on methicillin‐resistant Staphylococcus aureus (MRSA) using the broth microdilution method for activity assessment. The ethyl acetate fraction (S20b) had the strongest antibacterial activity against MRSA among the fractions tested. 14 compounds such as gallic acid and luteolin in S20b were analysed by UFLC‐Q‐TOF‐MS/MS. S20b combined with erythromycin showed synergy effects against MRSA and combined with ceftriaxone sodium and levofloxacin showed additive effects against MRSA. Electron microscopy showed that extract S20b damaged the MRSA cell wall and K+ efflux measurements indicated that extract S20b increased cell membrane permeability. Moreover, S20b suppression of PBP2a expression was assessed by Western blot. Furthermore, an in vivo study was used to investigate the therapeutic potential of S20b based on a mouse pneumonia model. Conclusions The in vitro study results have shown that S20b not only inhibits MRSA growth directly but also reduces the resistance of MRSA to the evaluated antibacterial agents. Based on the in vivo study, it can be concluded that S20b can treat pneumonia in the mouse model. Significance and Impact of the Study This study is the first research to demonstrate that S20b can inhibit MRSA growth and reduce drug resistance of clinical isolates to antibiotics. S20b has the potential to be used as a therapeutic agent against MRSA and treatment for MRSA pneumonia.