Mitochondrial stress as a conceptual interface between bacterial infection and post-infectious metabolic disease.

Mitochondria are central hubs integrating cellular bioenergetics, redox balance, innate immune signaling, and metabolic homeostasis. During bacterial infections, these organelles are recurrent targets of pathogen-derived toxins, secreted effectors, and host inflammatory mediators, leading to a state broadly defined as mitochondrial stress. This stress encompasses alterations in oxidative phosphorylation, mitochondrial dynamics, calcium handling, reactive oxygen species (ROS) production, and activation or disruption of mitochondrial quality control pathways such as mitophagy. In this perspective, we propose mitochondrial stress as a conceptual framework linking bacterial infection and post-infectious metabolic disease. Using enteric bacterial pathogens such as Salmonella enterica serovars Typhimurium and Typhi, together with Vibrio parahaemolyticus, as conceptual models, we synthesize current evidence showing how distinct bacterial strategies converge on mitochondrial dysfunction and immunometabolic reprogramming of host cells. We argue that, while mitochondrial stress responses may initially support antimicrobial defense, their incomplete resolution may contribute to long-lasting metabolic and inflammatory alterations in epithelial, immune, and metabolic tissues. Persistent mitochondrial dysfunction may contribute to insulin resistance, chronic inflammation, and increased susceptibility to metabolic disease after infection. By framing mitochondrial stress as a central integrator of infection and metabolism, this perspective highlights key knowledge gaps and identifies mitochondria-centered pathways as potential targets to prevent or mitigate post-infectious metabolic sequelae.