Abstract

Staphylococcus aureus is an important opportunistic pathogen of humans and animals. It produces extracellular vesicles (EVs) that are involved in cellular communication and enable inter-kingdom crosstalk, the delivery of virulence factors and modulation of the host immune response. The protein content of EVs determines their biological functions. Clarifying which proteins are selected, and how, is of crucial value to understanding the role of EVs in pathogenesis and the development of molecular delivery systems. Here, we postulated that S. aureus EVs share a common proteome containing components involved in cargo sorting. The EV proteomes of five S. aureus strains originating from human, bovine, and ovine hosts were characterised. The clustering of EV proteomes reflected the diversity of the producing strains. A total of 253 proteins were identified, 119 of which composed a core EV proteome with functions in bacterial survival, pathogenesis, and putatively in EV biology. We also identified features in the sequences of EV proteins and the corresponding genes that could account for their packaging into EVs. Our findings corroborate the hypothesis of a selective sorting of proteins into EVs and offer new perspectives concerning the roles of EVs in S. aureus pathogenesis in specific host niches.

Highlights

  • Staphylococcus aureus is an important opportunistic pathogen of humans and animals

  • In addition to extracellular vesicles (EVs), cylindrical structures were observed in the S. aureus Newbould 305 (N305), RF122, O11 and O46 samples (Supplementary Fig. S1)

  • The study of EVs produced by S. aureus is an emerging field of research, with pioneering work published in the late 2000s24

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Summary

Introduction

Staphylococcus aureus is an important opportunistic pathogen of humans and animals. It produces extracellular vesicles (EVs) that are involved in cellular communication and enable inter-kingdom crosstalk, the delivery of virulence factors and modulation of the host immune response. Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes a broad spectrum of infections in humans and animals In humans, these diseases range from superficial skin and soft tissue infections to life-threatening conditions that require hospitalisation and extensive medical support[1,2]. We postulated that S. aureus strains might share an EV proteome containing essential components for the cargo selection of proteins into EVs. Considering that secreted proteins are key elements in the virulence and host adaptation of S. aureus[27], we suggested that strains isolated from different hosts (human, bovine, ovine) and involved in different types of infection (from mild to severe) offer the best source of diversity to explore cargo selectivity and determine a robust core EV proteome. The distribution, functions, physicochemical properties and amino acid composition of the proteins packaged into EVs as a function of different strains were analysed and compared with regard to the host origin of strains, the severity of infections the strains produced could cause and the selectivity of protein cargo into EVs

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