title: Serum albumin disrupts Cryptococcus neoformans and Bacillus anthracis extracellular vesicles.
abstract: For both pathogenic fungi and bacteria, extracellular vesicles have been shown to contain many microbial components associated with virulence, suggesting a role in pathogenesis. However, there are many unresolved issues regarding vesicle synthesis and stability, including the fact that vesicular packaging for extracellular factors involved in virulence must also have a mechanism for vesicle unloading. Consequently, we studied the kinetics of vesicle production and stability using [1-(14) C] palmitic acid metabolic labelling and dynamic light scattering techniques. Cryptococcus neoformans vesicles were produced throughout all stages of fungal culture growth and they were stable once isolated. Density gradient analysis revealed that only a portion of the vesicle population carried cryptococcal polysaccharide, implying heterogeneity in vesicular cargo. Vesicle incubation with macrophages resulted in rapid vesicle instability, a phenomenon that was ultimately associated with serum albumin. Additionally, albumin, along with mouse serum and murine immunoglobulin destabilized Bacillus anthracis vesicles, but the effect was not observed with ovalbumin or keyhole limpet haemocyanin, demonstrating that this phenomenon is neither host-, microbe- nor protein-specific. Our findings strongly suggest that cryptococcal vesicles are short-lived in vivo and vesicle destabilization is mediated by albumin. The ability of albumin to promote vesicular offload through destabilization indicates a new activity for this abundant serum protein.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Wolf
authors.forename: Johanna
authors.initials: J
authors.lastname: Rivera
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000818:Animals; D001408:Bacillus anthracis / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000378:metabolism*; D007553:Isotope Labeling; D051379:Mice; D019308:Palmitic Acid / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D012709:Serum Albumin; D019308:Palmitic Acid