Song, Kunping and Chen, Li and Suo, Nanhua and Kong, Xinyi and Li, Juexi and Wang, Tianyu and Song, Lanni and Cheng, Mengwei and Guo, Xindian and Huang, Zhenghe and Huang, Zichen and Yang, Yixin and Tian, Xuechen and Choo, Siew Woh (2023) Whole-transcriptome analysis reveals mechanisms underlying antibacterial activity and biofilm inhibition by a malic acid combination (MAC) in Pseudomonas. PeerJ, 11. ISSN 2167-8359, DOI https://doi.org/10.7717/peerj.16476.
Full text not available from this repository.Abstract
Background. Pseudomonas aeruginosa is a highly prevalent bacterial species known for its ability to cause various infections and its remarkable adaptability and biofilmforming capabilities. In earlier work, we conducted research involving the screening of 33 metabolites obtained from a commercial source against two prevalent bacterial strains, Escherichia coli and Staphylococcus aureus. Through screening assays, we discovered a novel malic acid combination (MAC) consisting of malic acid, citric acid, glycine, and hippuric acid, which displayed significant inhibitory effects. However, the precise underlying mechanism and the potential impact of the MAC on bacterial biofilm formation remain unknown and warrant further investigation.Methods. To determine the antibacterial effectiveness of the MAC against Pseudomonas aeruginosa, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques were employed to observe bacterial morphology and biofilm formation. We further performed a biofilm inhibition assay to assess the effect of the MAC on biofilm formation. Whole-transcriptome sequencing and bioinformatics analysis were employed to elucidate the antibacterial mechanism of the MAC. Additionally, the expression levels of differentially expressed genes were validated using the real-time PCR approach.Results. Our findings demonstrated the antibacterial activity of the MAC against P. aeruginosa. SEM analysis revealed that the MAC can induce morphological changes in bacterial cells. The biofilm assay showed that the MAC could reduce biofilm formation. Whole-transcriptome analysis revealed 1093 differentially expressed genes consisting of 659 upregulated genes and 434 downregulated genes, in response to the MAC treatment. Mechanistically, the MAC inhibited P. aeruginosa growth by targeting metabolic processes, secretion system, signal transduction, and cell membrane functions, thereby potentially compromising the survival of this human pathogen. This study provides valuable insights into the antibacterial and antibiofilm activities of the MAC, a synergistic and cost-effective malic acid combination, which holds promise as a potential therapeutic drug cocktail for treating human infectious diseases in the future.
| Item Type: | Article |
|---|---|
| Funders: | Wenzhou-Kean University (5000105), Wenzhou Municipal Key Lab for Biomedical and Biopharmaceutical Informatics of Wenzhou-Kean University (20211227000125), Wenzhou Science and Technology "Qing Miao Project" |
| Uncontrolled Keywords: | Malic Acid; Antibacterial activity; Biofilm; Whole-transcriptome; Pseudomonas aeruginosa |
| Subjects: | Q Science > Q Science (General) Q Science > QH Natural history |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 09 Sep 2025 06:21 |
| Last Modified: | 09 Sep 2025 06:21 |
| URI: | http://eprints.um.edu.my/id/eprint/50576 |
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