Mitochondrial Dysfunction in Ehrlichia canis Infection

Transmitted by tick vectors, Ehrlichia canis (E. canis) is a Gram-negative, obligate intracellular bacterium of zoonotic concern that infects both canine and human hosts. Its pathogenesis centers on the targeting of mononuclear phagocytes, where it establishes an intracellular niche by suppressing phagolysosomal fusion and evading immune detection, thereby facilitating its replication. E. canis infection also compromises mitochondrial integrity, notably by disrupting the mitochondrial membrane potential (MMP, or ΔΨm), which triggers cellular stress and perturbs critical processes such as autophagy and apoptosis. The energy sensor AMP-activated protein kinase (AMPK), a central regulator of mitochondrial metabolism and cellular homeostasis, plays a critical role in mediating stress-responsive pathways, including those governing autophagy and apoptosis. This review examines the interplay between E. canis and host mitochondria, with a focus on AMPK-directed regulation of autophagy and apoptosis during infection. We summarize current knowledge on the mechanisms of mitochondrial dysfunction and AMPK signaling activation, and discuss the dual roles of autophagy and apoptosis in the pathogen's life cycle and disease progression. By delineating these molecular mechanisms, this review aims to advance the understanding of E. canis pathogenesis and inform future strategies for the control of canine monocytic ehrlichiosis (CME).