BolA affects the biofilm formation ability, outer membrane permeability and virulence, thus is required for the adaptability of Salmonella enterica serotype Typhimurium to the harsh survival environment

Abstract

Salmonella enterica serotype Typhimurium, an important foodborne pathogen with high adaptability to the host's internal and external survival environment, seriously threatens public health. Therefore, to understand the mechanism underlying the high adaptability, this study investigated the transcription factor BolA by constructing BolA deletion strain 269△BolA, complemented strain 269BolAR and overexpression strain 269BolA+ based on WT269. BolA significantly inhibited motility; at 6 h, the BolA overexpression strain (269BolA+) showed 91.2% and 90.7% lower motility than the wild type (WT269) and BolA deletion strain (269△BolA), respectively, by downregulating motility-related flagellar genes. BolA promoted biofilm formation; 269BolA+ showed 3.6-fold and 5.2-fold higher biofilm formation ability than WT269 and 269ΔBolA, respectively, by upregulation biofilm formation-related genes. BolA overexpression downregulated the outer membrane gene OmpF and upregulated OmpC, thereby regulating cell permeability, and reducing the antibacterial effect of vancomycin, which can destruct the outer membrane. BolA improved adaptability; 269△BolA showed higher susceptibility to eight antibiotics and 2.5- and 4-fold lower acid and oxidative stress tolerance, respectively, than WT269. In Caco-2 and HeLa cells, 269△BolA showed 2.8- and 3-fold lower cell adhesion ability, respectively, and 4- and 2-fold lower cell invasion ability, respectively, than WT269, through downregulation of the virulence genes. Thus, BolA expression promotes biofilm formation and balances the membrane permeability, thereby improving the resistance of the strains, and enhances its host cell invasion ability by upregulating bacterial virulence factors. Results of this study suggest that the BolA gene may serve as a potential target of therapeutic or preventative strategies to control Salmonella Typhimurium infections.