The combined administration of vancomycin and Zhenqi granules can improve the treatment of MRSA and its biofilms

Author:

Zhang Lulu1,Wen Bo1,Feng Xiaoyu1,Xia Yuwen1,Li Li1,Cheng Yungchi2,Jiang Chunyan3,Yang Weifeng1,Lu Cheng1,Tan Yong1

Affiliation:

1. China Academy of Chinese Medical Sciences

2. Yale University School of Medicine

3. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University

Abstract

Abstract

Background Methicillin-resistant Staphylococcus aureus (MRSA) biofilms significantly contribute to its resistance. Vancomycin (Van), a first-line antibacterial drug, struggles to inhibit these biofilms. Zhenqi granules (ZQ), a traditional Chinese medicine comprising Astragalus membranaceus and Ligustrum lucidum, enhance various the effectiveness of antimicrobial agents. This research aimed to decipher the effects and mechanisms of combining Van and ZQ on MRSA and its biofilms. Method The effect was examined through biofilm modelling and morphological observation. The underlying mechanism was explored by analysing key biofilm extracellular polymeric substances (EPS) like polysaccharide intercellular adhesion (PIA) and extracellular DNA (eDNA), and the second messenger c-di-AMP and its regulatory genes involved in wall teichoic acid (WTA) biosynthesis and K+ transport gating proteins. Results ZQ exhibits inhibits MRSA biofilm viability more effectively than Van. The combination therapy of Van and ZQ further impedes the growth of MRSA biofilms, reduces the fluorescence signal values of both live and dead bacteria, and alters bacterial morphology and size. This combined treatment also decreases c-di-AMP, PIA, and eDNA, inhibits icaA, ktrA, and demonstrates superior inhibition of fmtA and tarH compared to monotherapy. Conclusion The combination of Van and ZQ can effectively inhibit the growth of MRSA biofilm. The mechanism involves the reduction of c-di-AMP and the EPS components PIA and eDNA and the inhibition of the PIA synthesis gene icaA and the WTA genes fmtA, tarH. This study provides scientific evidence for the combination of Van and ZQ in the treatment of MRSA infection.

Publisher

Springer Science and Business Media LLC

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