Fig. 7.

Model of TssS-induced suppression of STING-mediated innate immunity. Yptb infection induces Mn²⁺ release from membrane-enclosed organelles into the cytosol of host cells, boosting activation of the cGAS-STING pathway. In host cells infected with Yptb WT (Left), the Mn²⁺-chelating micropeptide TssS was translocated into the cytosol via its T6SS. TssS suppresses the Mn²⁺-enhanced STING-mediated innate immune response by chelating Mn²⁺, thus reducing bacterial clearance. When host cells were infected with the ΔtssS mutant (Right), no Mn²⁺-chelating TssS was translocated, and the bioavailability of Mn²⁺ was higher. Consequently, STING and its downstream pathways were activated to a greater extent, restricting infection by the ΔtssS mutant.