Manganese scavenging and oxidative stress response mediated by type VI secretion system in .

Type VI secretion system (T6SS) is a versatile protein export machinery widely distributed in Gram-negative bacteria. Known to translocate protein substrates to eukaryotic and prokaryotic target cells to cause cellular damage, the T6SS has been primarily recognized as a contact-dependent bacterial weapon for microbe-host and microbial interspecies competition. Here we report contact-independent functions of the T6SS for metal acquisition, bacteria competition, and resistance to oxidative stress. We demonstrate that the T6SS-4 in is critical for survival under oxidative stress and is regulated by OxyR, a conserved oxidative stress regulator. The T6SS-4 is important for intracellular accumulation of manganese (Mn) under oxidative stress. Next, we identified a T6SS-4-dependent Mn-binding effector TseM, and its interacting partner MnoT, a Mn-specific TonB-dependent outer membrane transporter. Similar to the T6SS-4 genes, expression of is regulated by OxyR and is induced under oxidative stress and low Mn conditions. Both TseM and MnoT are required for efficient uptake of Mn across the outer membrane under Mn-limited and -oxidative stress conditions. The TseM-MnoT-mediated active Mn transport system is also involved in contact-independent bacteria-bacteria competition and bacterial virulence. This finding provides a perspective for understanding the mechanisms of metal ion uptake and the roles of T6SS in bacteria-bacteria competition.