Obligatory intracellular bacterium Anaplasma phagocytophilum AnkA regulates actin dynamics and spatiotemporal bacterial release

Author summary While cortical cytoskeleton serves as a barrier for exocytosis, how exocytic release of intra-vacuolar bacteria occurs through this barrier is poorly understood. Using obligatory intravacuolar bacteria Anaplasma phagocytophilum as a model, this study revealed it actively regulates exocytic bacterial release by deploying a type IV secretion effector, AnkA. Abundant AnkA is progressively secreted during bacterial growth and colocalized with cortical actin filaments. AnkA was found to interact with actin and actin regulatory proteins α-actinin 4 and gelsolin, thereby coordinated bacterial growth, cortical actin remodeling, and bacterial exocytosis. Sustained retention of A. phagocytophilum in nutritious intracellular niche is essential for bacterial replication, and timely extracellular release prior to demise of infected host cells is required for bacterial spreading for survival. This study revealed remarkable adaptation in obligatory intravacuolar pathogen by evolving a unique AnkA protein, providing a new paradigm of microbial pathogenesis by manipulation of spatiotemporal actin dynamics by a bacterial molecule.