Recently, the Animal’s Bacterial Infectious Diseases Innovation Team of Shanghai Veterinary Research Institute (SHVRI) found that the ferric uptake regulator (Fur) directly represses the expression, secretion and function of type VI secretion system (T6SS) function in Salmonella enterica serovar Typhimurium (S. Typhimurium). This study revealed a novel regulatory mechanism of T6SS in S. Typhimurium, thus help to elucidate the mechanisms of bacterial adaptability and virulence. These results were published online on August 5, 2019 in Infection and Immunity.

During infection, hosts could inhibit the bacterial survival by limiting the nutritional components. While pathogens use several common strategies to compete with other species and accomplish systemic infections. T6SSs are highly conserved and complex protein secretion systems that deliver effector proteins into eukaryotic hosts or other bacteria.T6SS is a highly conserved protein secretion system in bacteria, which secretes effector proteins acting on eukaryotic hosts or other bacteria. A T6SS within Salmonella pathogenicity island 6 (SPI-6) is activated during infection, and it contributes to the pathogenesis as well as interbacterial competition of S. Typhimurium. This study found that T6SS core gene clpV expression is upregulated during infection and under iron depleted conditions, suggesting that T6SS contributes to the pathogenesis of S. Typhimurium. Moreover, the global regulator Fur was shown to repress the clpV expression and T6SS secretion in the iron-replete medium. Furthermore, electrophoretic mobility shift and DNase I footprinting assays revealed that Fur could binds directly to the clpV promoter region at multiple sites spanning the transcriptional start site. We also observed that the relieving of Fur-mediated repression on the clpV contributed to the interbacterial competition activity and pathogenicity of S. Typhimurium. These findings provide insights into the directly regulation of Fur on the expression and functional activity of SPI-6 T6SS in S. Typhimurium, thus help to elucidate the mechanisms of bacterial adaptability and virulence.

The first author of this paper is Associate Professor Shaohui Wang, the corresponding author is Professor Shengqing Yu, the chief of Animal’s Bacterial Infectious Diseases Innovation Team of SHVRI. This research was funded by the National Natural Science Foundation of China and the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences.
Paper link: http://iai.asm.org/cgi/pmidlookup?view=long&pmid=31383745