AUTHOR=Zhang Rui , Tian Shuo , Zhang Tengfei , Zhang Wenting , Lu Qin , Hu Qiao , Shao Huabin , Guo Yunqing , Luo Qingping 

TITLE=Antibacterial activity mechanism of coptisine against Pasteurella multocida

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1207855

DOI=10.3389/fcimb.2023.1207855

ISSN=2235-2988

ABSTRACT=Pasteurella multocida is a widespread zoonotic pathogen that causes severe damage to the poultry industry. This study focused on the antibacterial effects and mechanism of action of coptisine against P. multocida. We demonstrated that coptisine has a strong antibacterial effect against P. multocida, with a minimum inhibitory concentration of 0.125 mg/mL. Moreover, the measurement of the half maximal inhibitory concentration confirmed that coptisine was safe for the pathogen. The growth curve showed that coptisine inhibited bacterial growth. Measurement of alkaline phosphatase activity in the culture solution showed that coptisine affected cell wall permeability. Transmission electron microscopy revealed that coptisine chloride destroyed the cell structure. In addition, coptisine blocked the respiratory system, as measured by the levels of critical enzymes of the tricarboxylic acid cycle and glycolysis, succinate dehydrogenase and lactate dehydrogenase, respectively.Similarly, coptisine inhibited the synthesis of soluble proteins and genomic DNA. Finally, the effect of coptisine on gene transcription was measured using RNA sequencing. The KEGG pathway analysis of the differentially expressed genes showed that they were associated with cellular, respiratory, and amino acid metabolism, which were downregulated after coptisine treatment.Additionally, genes related to RNA degradation and the aminoacyl-tRNA pathway were upregulated.These findings suggest that coptisine has a multifaceted impact on various pathways, resulting in the inhibition of P. multocida. Thus, coptisine is a potential alternative to antibiotics for the treatment of P. multocida infections in a clinical setting.