Bacterial pathogens hijack host cell peroxisomes for replication vacuole expansion and integrity.

Abstract

Pathogens manipulate host cell organelles to establish infection. There is extensive evidence of pathogen modulation of the endoplasmic reticulum, Golgi apparatus, mitochondria, endosomes, lysosomes, and nucleus. However, one organelle that has been largely overlooked in connection with bacterial pathogenesis is peroxisomes. Here, we demonstrate that <i>Legionella</i> actively recruits peroxisomes to its replication vacuole using a secreted bacterial effector protein. Defects in peroxisome metabolic function restrict expansion of the <i>Legionella</i> vacuole membrane and cause rupture of this compartment, inhibiting bacterial replication and leading to bacterial degradation. Similarly, peroxisome dysfunction causes <i>Salmonella</i> replication vacuole destabilization and reduced bacterial burden within host cells. Thus, these two intracellular bacterial pathogens exploit host cell peroxisomes to maintain their replication compartments, establishing a critical role for this organelle in disease.