A complex of membrane vesicles and amyloids reflects environmental stresses in Staphylococcus aureus.

Staphylococcus aureus releases extracellular membrane vesicles (MVs) that exert diverse biological functions depending on their cargo. Moreover, MV cargos can be reprogrammed in response to different growth conditions. In this study, we aimed to investigate whether the protein cargo in MVs can reflect specific environmental stresses, including iron depletion and antibiotic exposure, which S. aureus may encounter during infection. Unexpectedly, we found that extensive fibrillar amyloids were co-purified with S. aureus MVs when iron was depleted from the medium. This phenotype was also observed in bacteria grown in normal medium, albeit to a much lesser extent, and displayed distinct characteristics under antibiotic-treated conditions. To further elucidate the relationship between this phenotype and environmental stresses, we compared the proteomes of the MV-amyloid complexes derived from S. aureus cultured under the aforementioned conditions. Our results revealed stress-specific proteomic alterations in the MV-amyloid complex, as demonstrated by functional enrichment analyses of differentially expressed proteins. In summary, our findings demonstrate for the first time that amyloid formation, similar to MV production, is regulated by environmental stresses. The stress-specific proteomic changes of the MV-amyloid complex suggest a potential role for this complex in the environmental adaptation of S. aureus.