Impact of Deoxynivalenol on the Evolution of Drug Resistance in Bacillus cereus

In vitro experiments with deoxynivalenol (DON) exposure have confirmed that Bacillus cereus isolated from preparations, after being treated with DON, developed into multidrug-resistant strains, suggesting that under DON contamination, probiotics may transform into carriers for the dissemination of drug resistance. Transcriptomic analysis revealed that significantly differentially expressed genes in the resistant strains were enriched in pathways such as cell wall synthesis, quorum sensing, and ABC transporters. Functional overexpression validation of the cell wall synthesis-related gene lrgA found that the standard strain of Bacillus cereus, the primary strain PA28B1, and the standard strain of Bacillus subtilis all exhibited significant tolerance to meropenem, an antibiotic targeting the cell wall, with a 64-fold increase in the minimum inhibitory concentration (MIC) value. This reveals the molecular mechanism by which DON drives the evolution of drug resistance through upregulation of cell wall synthesis-related gene expression and facilitates cell wall structural remodeling. Additionally, DON exposure also activated the expression of reactive oxygen species (ROS)-related genes in resistant strains and increased their ROS levels and cell membrane permeability, suggesting that the ROS signaling pathway may synergistically participate in the evolution of drug resistance.