Biological Effect of Streptococcus pyogenes-Released Extracellular Vesicles on Human Monocytic Cells, Induction of Cytotoxicity, and Inflammatory Response
Kazunori Murase, Chihiro Aikawa, Takashi Nozawa, Ayako Nakatake, Kuniyo Sakamoto, Taisei Kikuchi, Ichirô Nakagawa
Abstract
Most bacteria naturally release spherical lipid-bilayered extracellular vesicles (EVs) containing proteins, nucleic acids, and virulence-related molecules, thus contributing to diverse biological functions including transport of virulence factors. The group A streptococcus, Streptococcus pyogenes (GAS), a major human pathogen, also releases EVs; however, it remains unclear how GAS EVs interact physiologically and pathologically with host cells, and what the differences are between invasive and non-invasive strains. The proteome profile in this study revealed that GAS EVs enclosed many virulence-related proteins such as streptolysin O and NAD-glycohydrolase, facilitating their pathogenicity, and invasive GAS EVs were more abundant than non-invasive counterparts. In terms of biological effects, invasive GAS EVs showed slo -dependent cytotoxic activity and the induction of cytokine expression, contributing to GAS pathogenicity directly. Although non-invasive GAS EVs did not show cytotoxic activity, they may be utilized as a means to prevent antibacterial mechanisms such as autophagy, leading to enhancement of their own survival in the intracellular environment after the infection. These results suggest that invasive and non-invasive GAS EVs play different roles in GAS infection strategy and pathogenicity. Our findings also indicate that EVs could be a key factor for GAS pathogenicity in GAS-host interactions.