image: A-J, Longitudinal central sections of the PVC density maps for the three samples in the baseplate (A-E) and sheath-tube trunk (F-J) regions. For the PVC-Pnf and PVC-Pdp1 samples, cargo densities are highlighted in blue and cyan, respectively, and are displayed at a contour level of 3σ (B, G, D, I) or 1σ (C, H, E, J) level.
Contractile injection systems (CISs) are widely distributed in bacteria and archaea that can form a nanomachine resembling the contractile tails of bacteriophage (T4, P2, etc.) to translocate proteins and nucleic acids . The P. asymbiotica was shown to be involved in the human infection with severe skin lesions. The PVC loci within P. asymbiotica genome produce molecular needle complexes and encode several putative effector genes. It would be a candidate P. asymbiotica weapon that participates in the attack of mammalian cells, but substantial evidences will be needed to verify this hypothesis.
In this study, researchers have characterized the PAU_RS16575 as a potent PVC effector, which is widely present in bacteria. This toxin (designated as Pdp1, Photorhabdus dNTP pyrophosphatase 1) is responsible for the cytotoxicity towards the eukaryotic cells on the basis of its dNTP pyrophosphatase activity.Meanwhile, researchers have shown that the PVC effector Pdp1, together with Pnf that has been investigated before, could be loaded and translocated directly into the mammalian macrophage through PVC complex to induce cell death.
Besides, the loading scenario of PVC effectors Pdp1 and Pnf are demonstrated by cryo-EM detection and the targeting cells of PVC are determined. The direct translocation of the effectors by PVC is also validated by in vitro experiments.
These molecular nanosyringes show potential for biotechnology application in delivering drugs or proteins into eukaryotic hosts and this work sets the foundation for further investigations of the PVC-related eCISs and their effectors.