AUTHOR=Qiao Hu , Tengfei Zhang , Wenting Zhang , Qin Lu , Yunqing Guo , Xiaoyi Cao , Huabin Shao , Xinguo Zhai , Qingping Luo 

TITLE=Mechanistic insights of magnolol antimicrobial activity against Mycoplasma using untargeted metabolomic analyses

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1325347

DOI=10.3389/fcimb.2023.1325347

ISSN=2235-2988

ABSTRACT=<p>The unreasonable use of antibiotics is one of the important causes of antimicrobial resistance (AMR) that poses a huge public health threat. Magnolol is a traditional Chinese medicine exhibiting antibacterial-, antifungal-, anti-inflammatory-, and antioxidant activities. However, it is unclear whether magnolol has an inhibitory effect on <italic>mycoplasma</italic>. This study found that magnolol showed excellent inhibitory activity against various mycoplasmas. Magnolol showed dose-dependent inhibition of <italic>Mycoplasma synoviae</italic> growth and biofilm formation <italic>in vitro</italic>. Magnolol caused severely sunken and wrinkled <italic>M. synoviae</italic> cell membranes at the minimum inhibitory concentration, and an enlarged cell diameter. The chicken embryo infection model showed that magnolol significantly reduced <italic>M. synoviae</italic> pathogenicity <italic>in vivo</italic>. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the citrate cycle, glycolysis/gluconeogenesis, and pyruvate metabolism were significantly disturbed at the minimum inhibitory concentration of magnolol. Interestingly, 41% of differential metabolites were in the categories of lipids and lipid-like molecules. Protegenin A was up-regulated 58752-fold after magnolol treatment. It belongs to fatty acyls, and destroys cell membrane integrity and cell activity. Ghosphatidylethanolamine, phosphatidylglycerol, phosphatidic acid, and phosphatidylserine related to membrane maintenance and stress response were widely down-regulated. Collectively, our results illustrate the feasibility of magnolol as a phytochemical compound to treat mycoplasma infection.</p>