Reciprocal regulation between bacterial secretion systems and host metabolism: Enhancing bacterial intracellular survival capability

Secretion systems are intricate nanomachines present on many bacterial cell membranes that deliver various bacterially-encoded effector proteins into eukaryotic or prokaryotic cells. They are pivotal in bacterial invasion, host colonization, and pathogenesis. After infection, bacteria employ these machines to deliver toxic effectors to the cytoplasm of host cells that disrupt their metabolic balance, such as interfering with glucose metabolism, promoting lipid droplets formation, altering amino acid profiles and mitochondrial morphology, and reducing ROS levels, to ensure bacterial intracellular survival. Furthermore, metabolites within host cells can modulate the expression and/or function of bacterial secretion systems. This review summarizes recent advancements in understanding the impact of bacterial secretion systems on host cell metabolism and the feedback regulation of host metabolites on these machines, providing novel perspectives on host-pathogen interactions and mechanisms of bacterial pathogenesis.