Temporal RNAseq D. discoideum M. marinum infection
M. tuberculosis infection remains a major global health concern. Using Dictyostelium discoideum as a model organism to study Mycobacterium marinum infection, this study highlights evolutionarily conserved pathways relevant to human macrophages. It uncovers global and time-specific host response pathways across different stages of infection, revealing distinct gene regulation within the autophagy and ESCRT machinery pathways, which are critical for cellular responses to intracellular pathogens. Importantly, we identify Atg9 as a host resistance factor that protects against mycobacterial infection by preserving the MCV integrity and preventing early bacterial escape into the cytosol. Through its involvement in membrane damage responses, Atg9 limits access of virulent bacteria to a permissive cytosolic replicative niche, thereby limiting intracellular proliferation. The strong similarity between Dd and human macrophage responses, particularly in the later stages of infection, underscores Dd's value as a model for mycobacterial research. Furthermore, these findings identify membrane repair, possibly via ATG8ylation, and Atg9-dependent xenophagic bacterial restriction as distinct host defense mechanisms, providing new mechanistic insight and highlighting potential therapeutic targets for tuberculosis.
BioProject