ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
Antifungal mechanism and transcriptome analysis of Bacillomycin D-C16 against Fusarium oxysporum
Provisionally accepted
- 1Xuzhou Medical University, Xuzhou, China
- 2Nanjing Agricultural University, Nanjing, China
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Abstract: Fusarium oxysporum is a globally distributed soil-borne pathogen that causes substantial economic losses in cash crops. In this study, Bacillomycin D-C16, a natural antimicrobial lipopeptide produced by Bacillus subtilis, exhibited potent fungicidal activity against F. oxysporum, with a minimum inhibitory concentration (MIC) of 8 mg/L. Transmission electron microscopy (TEM) revealed that Bacillomycin D-C16 induced structural disruption of mitochondria in F. oxysporum. Transcriptome analysis identified 3,370 differentially expressed genes (DEGs) in F. oxysporum exposed to 8 mg/L Bacillomycin D-C16, comprising 1,488 up-regulated and 1,882 down-regulated genes. Cluster analysis revealed significant changes in gene expression patterns: DEGs associated with mitochondrial function [including oxidative phosphorylation and citrate cycle (TCA cycle) pathways] were down-regulated, while most DEGs involved in glutathione metabolism were up-regulated. Furthermore, nearly all DEGs related to DNA replication were significantly suppressed. Biochemical assays confirmed these observations: Reduced activities of mitochondrial enzymes [malate dehydrogenase (MDH), isocitrate dehydrogenase (IDH), pyruvate dehydrogenase (PDH), and complexes I–V], decreased mitochondrial membrane potential, and diminished ATP content collectively indicated mitochondrial dysfunction. Depleted glutathione (GSH) levels accompanied by elevated glutathione s-transferase (GST) activity, increased malondialdehyde (MDA) content, and accumulated reactive oxygen species (ROS) confirmed disruptions in glutathione metabolism and oxidative stress. Ultraviolet (UV) absorption spectra, fluorescence spectroscopy, and molecular docking simulations demonstrated Bacillomycin D-C16's preferential binding to the major groove of DNA, leading to abnormal DNA replication. These findings collectively demonstrate that Bacillomycin D-C16 inhibits F. oxysporum growth through multifaceted mechanisms involving transcriptional regulation, mitochondrial impairment, ROS accumulation, and interference with DNA replication.
Keywords: Bacillomycin D-C16, Fusarium oxysporum, Transcriptome, Mitochondrial dysfunction, ROS accumulation, DNA binding
Received: 04 Sep 2025; Accepted: 31 Oct 2025.
Copyright: © 2025 Lin, Jiao, Jiang, Zheng, Wu, Zhou, Ren, Lu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuanhong Li, lyh@xzhmu.edu.cn
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