A Legionella effector modulates host cytoskeletal structure by inhibiting actin polymerization

Area of Science:

• Microbiology
• Cell Biology
• Pathogenesis

Background:

• Legionella pneumophila is an opportunistic pathogen requiring numerous virulence proteins for infection.
• These proteins are delivered via the Dot/Icm type IV secretion system to manipulate host cells.
• A key target is the creation of the Legionella-containing vacuole (LCV) for bacterial replication.

Purpose of the Study:

• To investigate the function of the Dot/Icm substrate Ceg14 (Lpg0437).
• To determine the role of profilin in mitigating Ceg14-induced toxicity.
• To elucidate the mechanism by which Ceg14 affects host cell processes, particularly the cytoskeleton.

Main Methods:

• Yeast toxicity assays to assess Ceg14 effects.
• Genetic manipulation of profilin to study its interaction with Ceg14.
• Analysis of actin distribution and polymerization in response to Ceg14 expression.
• Biochemical assays including co-sedimentation with filamentous actin.

Main Results:

• Ceg14 exhibits toxicity in yeast, which is suppressed by profilin overexpression.
• Profilin mutations affecting actin binding, but not other interactions, abolish this suppressor activity.
• Ceg14 expression disrupts actin distribution and cell budding in yeast.
• Ceg14 inhibits actin polymerization and causes accumulation of short actin filaments, without direct interaction with profilin.

Conclusions:

• Ceg14 is a Legionella pneumophila effector that targets and disrupts the host actin cytoskeleton.
• Profilin plays a crucial role in counteracting Ceg14's detrimental effects on the cytoskeleton.
• These findings highlight a conserved mechanism where L. pneumophila effectors target host cytoskeletal components for successful infection.