A unique bacterial secretion machinery with multiple secretion centers.

Area of Science:

• Microbiology
• Structural Biology
• Bacterial Pathogenesis

Background:

• The type IX secretion system (T9SS) in Porphyromonas gingivalis is essential for secreting virulence factors like gingipains, contributing to periodontal disease.
• Understanding the T9SS structure and mechanism is key to developing therapeutic strategies against this pathogen.

Purpose of the Study:

• To elucidate the high-resolution structure and assembly of the Porphyromonas gingivalis type IX secretion system (T9SS).
• To understand the functional mechanism of substrate translocation across the outer membrane.

Main Methods:

• In situ cryoelectron tomography was employed to visualize the T9SS structure within P. gingivalis.
• Analysis of protein-protein interactions and conformational changes of T9SS components.

Main Results:

• The P. gingivalis T9SS comprises 18 PorM dimers forming a periplasmic ring, interacting with a PorKN ring complex near the outer membrane.
• Proton motive force energizes PorMKN translocation complexes, indicating distinct activation states.
• A 12-fold symmetric cytoplasmic complex involving PorM and PorL is required for assembly at the inner membrane.
• Substrates are translocated across the outer membrane via eight Sov translocons arranged in a ring.

Conclusions:

• The T9SS assembles as a unique supramolecular machine with distinct motor and export pore components.
• This structural and mechanistic insight provides a foundation for targeting the T9SS in P. gingivalis infections.