Biogenesis and function of extracellular vesicles in gram-positive bacteria, mycobacteria, and fungi

The production of membrane vesicles (MVs) has been documented in all domains of life. Justification for the historical lack of interest in the study of vesicle biogenesis in Gram-positive bacteria, mycobacteria, and fungi is based on the difficulty in explaining how MV can traverse the thick cell wall. For this reason, the scientific landscape has been dominated by studies examining vesicle biogenesis in microorganisms that lack cell walls or Gram-negative bacteria, since they possess an outer membrane layer. Evidence of MV production by cell-walled microorganisms is now available from different experimental approaches including, isolation of MVs from culture supernatant, compositional analysis, visualization of vesiculation events, and genetic studies. Strikingly, more recent studies have shown that beside the fundamental differences in the architecture of the cell envelope of Gram-positive and Gram-negative bacteria, a similar mechanism of cell wall remodeling may govern the release of MVs. Here, we describe the current understanding of vesicle biogenesis in cell-walled microorganisms, discussing novel mechanisms of vesicle production, methods to study MVs, cargo, and functions of MVs as well as medical applications of naturally produced MVs.