The Mutation of the DNA-Binding Domain of Fur Protein Enhances the Pathogenicity of Edwardsiella piscicida via Inducing Overpowering Pyroptosis

• Published in: Microorganisms (Basel) Vol. 12; no. 1; p. 11
• Main Authors: Niu, Mimi, Sui, Zhihai, Jiang, Guoquan, Wang, Ling, Yao, Xuemei, Hu, Yonghua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.12.2023; MDPI
• Subjects: Amino acids; Aquaculture; Bacteria; Binding; Biofilms; Cytotoxicity; Deoxyribonucleic acid; Dimerization; DNA; E coli; Economic impact; Edwardsiella piscicida; ferric uptake regulator; fish pathogen; Functional analysis; Fur protein; Genomes; Gram-positive bacteria; Heat resistance; High temperature; Homeostasis; Lethality; Macrophages; Manganese; Motility; Mutants; Mutation; N-terminal domain; Pathogenicity; Pathogens; Phagocytes; Phenotypes; Proteins; Pyroptosis; Regulatory mechanisms (biology); Resistance factors; stress tolerance; Temperature tolerance; Virulence; Beijing China; United States > US; China; stress tolerance; N-terminal domain; virulence; ferric uptake regulator; fish pathogen
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms12010011

is an important fish pathogen with a broad host that causes substantial economic losses in the aquaculture industry. Ferric uptake regulator (Fur) is a global transcriptional regulator and contains two typical domains, the DNA-binding domain and dimerization domain. In a previous study, we obtained a mutant strain of full-length of , TX01Δ , which displayed increased siderophore production and stress resistance factors and decreased pathogenicity. To further reveal the regulatory mechanism of Fur, the DNA-binding domain (N-terminal) of Fur was knocked out in this study and the mutant was named TX01Δ 2. We found that TX01Δ 2 displayed increased siderophore production and enhanced adversity tolerance, including a low pH, manganese, and high temperature stress, which was consistent with the phenotype of TX01Δ . Contrary to TX01Δ , whose virulence was weakened, TX01Δ 2 displayed an ascended invasion of nonphagocytic cells and enhanced destruction of phagocytes via inducing overpowering or uncontrollable pyroptosis, which was confirmed by the fact that TX01Δ 2 induced higher levels of cytotoxicity, IL-1β, and p10 in macrophages than TX01. More importantly, TX01Δ 2 displayed an increased global virulence to the host, which was confirmed by the result that TX01Δ 2 caused higher lethality outcomes for healthy tilapias than TX01. These results demonstrate that the mutation of the Fur N-terminal domain augments the resistance level against the stress and pathogenicity of , which is not dependent on the bacterial number in host cells or host tissues, although the capabilities of biofilm formation and the motility of TX01Δ 2 decline. These interesting findings provide a new insight into the functional analysis of Fur concerning the regulation of virulence in and prompt us to explore the subtle regulation mechanism of Fur in the future.