6/9 Using a murine sepsis model of Streptococcus pneumoniae infection, we show that p97 limits bacterial proliferation in vivo and protects the host from septic shock, highlighting its crucial role in immune defence.

5/9 Using in-vitro reconstitution, optical traps & electron microscopy, we reveal that p97 uses ATP-driven force to extract bacterial surface proteins, in turn ripping apart the pathogen, releasing their internal contents.

4/9 Our findings reveal four key criteria that dictates p97’s recruitment to bacterial surfaces: (1) Cytosolic exposure, (2) K48-polyUb modification, (3) Presence of ubiquitinable substrates, (4) Recognition by ubiquitin binding cofactors, in this case NPLOC4-UFD1.

3/9 We discovered that host cell unleashes a tweezer-like nanomachine, 🔥VCP/p97🔥, which plucks out these ubiquitinated proteins from bacterial surfaces to disintegrate them and halt infection at its core.

🚨“Ripping bacteria to shreds” 🚨 VCP/p97, a cellular AAA-ATPase, targets and then using its tweezer like action rips apart bacteria, protecting us from infections. A thread 🦠💥#MolecularMachines #HostDefense #cellularimmunity #microbiology
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