This web page was created programmatically, to learn the article in its authentic location you possibly can go to the hyperlink bellow: https://www.nature.com/articles/s42003-026-10543-yand if you wish to take away this text from our website please contact us [ad_1] Francisella tularensis, a gram-negative facultative intracellular pathogen, causes the often-fatal illness tularemia. Its Francisella pathogenicity island (FPI) encodes a kind VI secretion system (T6SS) important for virulence, but the mechanisms by which T6SS effectors allow intracellular replication stay poorly understood. Here, we report the construction of the T6SS effector PdpC, revealing a novel protein fold with no identifiable homologs. The construction resembles a seahorse, comprising 5 domains: an N-terminal area, a central physique area (CBD), a wedge area, a C-terminal tail, and an unmodeled “mouth” area. Biochemical analyses reveal that PdpC binds host phospholipids, notably phosphatidylinositol-3-phosphate, and interacts with PdpE, one other FPI-encoded protein. Structure-guided purposeful research present that the CBD alone suffices for these interactions, whereas PdpE is secreted through a T6SS-independent pathway. These findings clarify how the delicate effector duo permits phagosomal escape and establishes an infection: PdpC is delivered by T6SS to PI(3)P-enriched early phagosomal membranes to rupture phagosomes to flee, after which coordinates with PdpE to advertise intracytoplasmic Francisella replication. This work transforms PdpC from an orphan virulence issue right into a tractable molecular swap on the coronary heart of Francisella’s intracellular way of life and a possible goal for anti-tularemia therapeutics. [ad_2] This web page was created programmatically, to learn the article in its authentic location you possibly can go to the hyperlink bellow: https://www.nature.com/articles/s42003-026-10543-yand if you wish to take away this text from our website please contact us