A Fur-regulated type VI secretion system contributes to oxidative stress resistance and virulence in Yersinia pseudotuberculosis

Abstract

The type VI secretion system (T6SS) is a widespread protein secretion apparatus deployed by many Gram-negative bacterial species to interact with competitor bacteria, host organisms, and the environment. Yersinia pseudotuberculosis T6SS4 was recently reported to be involved in manganese acquisition; however, the underlying regulatory mechanism still remains unclear. In this study, we discovered that T6SS4 is regulated by ferric uptake regulator (Fur) in response to manganese ions (Mn²⁺), and this negative regulation of Fur was proceeded by specifically recognizing the promoter region of T6SS4 in Y. pseudotuberculosis. Furthermore, T6SS4 is induced by low Mn²⁺ and oxidative stress conditions via Fur, acting as a Mn²⁺-responsive transcriptional regulator to maintain intracellular manganese homeostasis, which plays important role in the transport of Mn²⁺ for survival under oxidative stress. Our results provide evidence that T6SS4 can enhance the oxidative stress resistance and virulence for Y. pseudotuberculosis. This study provides new insights into the regulation of T6SS4 via the Mn²⁺-dependent transcriptional regulator Fur, and expands our knowledge of the regulatory mechanisms and functions of T6SS from Y. pseudotuberculosis.

Funding

National Key R&D Program of China ,(2018YFA0901200); National Natural Science Foundation of China,(32100149); Postdoctoral Research Foundation of China,(2020M673501); Scientific Startup Foundation for Doctors of Northwest A and F University,(Z1090122002); Young Talent Support Program of Shaanxi Province University,(20220206)