Downregulation of Ribosomal Contents and Kinase Activities Is Associated with the Inhibitive Effect on the Growth of Group B Streptococcus Induced by Placental Extracellular Vesicles.

Abstract

Simple SummaryThe bioactive properties of extracellular vesicles (EVs) in the physiological and pathophysiological conditions of pregnancy and cancers have been well investigated. However, the interaction of EVs and bacterial cells has not been studied yet. Transferring and releasing of cargos in EVs intracellularly impact the function of target cells. In this study, we investigated the effect of placental EVs on the growth of opportunistic pathogens such as Group B Streptococcus (GBS), which is a major cause of some complications of pregnancy. We found that placental micro-EVs or nano-EVs attenuated the growth of a Gram-positive bacterium, GBS. This attenuative effect at least partially required an interaction of placental EVs with GBS. Proteomic analysis showed that changes in protein synthesis or cellular energy in GBS may contribute to this inhibitory effect.Background: Like many other cell types, the human placenta produces large amounts of extracellular vesicles (EVs). Increasing evidence has shown that placental EVs contribute to the regulation of maternal immune and vascular systems during pregnancy via the transfer of their cargos. In this study, we investigated the effect of placental EVs on the growth of opportunistic pathogens that commonly colonise the female reproductive tract. Methods: Gram-positive bacterium Group B Streptococcus (GBS) and Gram-negative bacterium Escherichia coli (E. coli) were treated with placental EVs that were collected from placental explant cultures, and the growth, susceptibility, and resistance to antibiotics of the bacteria were measured. In addition, comparative proteomics analysis was also performed for the GBS with or without exposure to placental EVs. Results: When treated with placental micro-EVs or nano-EVs, the GBS growth curve entered the stationary phase earlier, compared to untreated GBS. Treatment with placental EVs also inhibited the growth of GBS on solid medium, compared to untreated GBS. However, these biological activities were not seen in E. coli. This attenuative effect required interaction of placental EVs with GBS but not phagocytosis. In addition, the susceptibility or resistance to antibiotics of GBS or E. coli was not directly affected by treatment with placental EVs. The proteomic and Western blotting analysis of GBS that had been treated with placental EVs suggested that the downregulation of cellular components and proteins associated with phosphorylation and cell energy in GBS may contribute to these attenuative effects. Conclusion: We demonstrated the attenuative effect of the growth of GBS treated with placental EVs. Downregulation of cellular components and proteins associated with phosphorylation and cell energy may contribute to the physiological changes in GBS treated with placental EVs.