More than just membranes: membrane contact sites as crossroads for infections.

Membrane contact sites (MCSs), tethering zones between organelles, have emerged as critical hubs for regulating cellular metabolism, homeostasis, and immune responses. Recent discoveries reveal that a wide range of intracellular pathogens, including bacteria, viruses, parasites, and fungi, exploit MCSs to establish and maintain their replicative niches within host cells. By co-opting the host MCS machinery, these pathogens create specialized interfaces between their vacuoles, replication complexes, or cytosolic domains and host organelles, enabling nutrient acquisition, immune evasion, and spatial signaling. This review highlights how intracellular pathogens, such as Salmonella and others, subvert MCS architecture and function. Furthermore, emerging concepts and tools in the study of pathogen-MCS interactions are discussed, along with how these insights influence the development of host-directed therapies against infectious diseases.