Intact and Degenerate Diguanylate Cyclases regulate Shigella Cyclic di-GMP

Area of Science:

• Microbiology
• Molecular Biology
• Bacterial Pathogenesis

Background:

• Shigella is an intracellular pathogen causing dysentery.
• Bacterial adaptation to host environments relies on second messenger signaling systems.
• Cyclic di-GMP (c-di-GMP) is a key second messenger synthesized by diguanylate cyclases (DGCs).

Approach:

• Investigated the role of individual Shigella flexneri DGCs in c-di-GMP synthesis and pathogenesis.
• Expressed intact DGCs in a DGC-deleted strain to assess c-di-GMP production and phenotypes.
• Analyzed the contribution of both intact and degenerate DGCs to c-di-GMP signaling.

Key Points:

• Four intact S. flexneri DGCs synthesize c-di-GMP at varying levels in vitro and during host cell infection.
• Expression of dgcF and dgcI reduces bacterial invasion and plaque formation, with dgcF increasing acid sensitivity.
• Degenerate DGC genes (dgcE, dgcQ, dgcN) with nonsense mutations also produce c-di-GMP, suggesting complex signaling pathways.

Conclusions:

• Both intact and degenerate DGCs contribute to S. flexneri c-di-GMP signaling.
• Phenotypes associated with dgcF and dgcI expression do not always correlate with measured c-di-GMP levels.
• The study highlights the multifaceted role of DGCs in Shigella pathogenesis and adaptation.