Microbe-induced migrasome-like structures and their role in microbial persistence, immune evasion and transmission

Microbial pathogens have evolved sophisticated strategies to disseminate within hosts, yet the full repertoire of intercellular transmission routes remains incompletely understood. Traditional models of microbial spread emphasize free-particle diffusion and direct cell-to-cell contact. Here, we extend our recently proposed "vimig" concept, originally confined to viruses, into a unifying framework of "microbe-induced migrasome-like structures" (mMig) that encompasses viruses, bacteria, and mycoplasmas. These migrasomes act as microbial Trojan horses, encapsulating intact pathogens together with host cellular debris. Functionally, mMig confers three cardinal pathogenic advantages: it enables receptor-independent entry into otherwise non-permissive cells; it supports non-lytic egress, allowing collective en bloc transmission while preserving host cell integrity; and it shields pathogens from immune attack and antimicrobial action, as mMig-encapsulated microbes resist antibody neutralization and antibiotic clearance. We examine how microbes exploit host factors to drive mMig biogenesis, and identify zinc ions as a natural dietary inhibitor of this pathway. Beyond dissemination, toxin-induced non-canonical migracytosis triggers rapid inflammatory responses, directly linking mMig to immunopathology. This review systematically catalogs ten viruses, large clostridial toxins (LCTs) produced by Clostridia, and Mycoplasma that induce mMig, compares three structural types (migrasome, retractosome, and migrion), and critically assesses host-directed interventions as potential broad-spectrum antimicrobial tools that could circumvent conventional resistance. Redefining these pathogen-induced vesicles as a conserved Achilles' heel in host-microbe interactions, we propose that targeted inhibition of mMig biogenesis offers a paradigm-shifting opportunity to combat refractory infections and alleviate infection-associated immunopathology.