Staphylococcus aureus Extracellular Vesicles: A Story of Toxicity and the Stress of 2020

Xiaogang Wang,Olivia F English,Jean C Lee,Paul F Koffi

doi:10.3390/toxins13020075

Xiaogang Wang, Olivia F English + Show 2 more

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https://doi.org/10.3390/toxins13020075

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Journal: Toxins	Publication Date: Jan 20, 2021
Citations: 37	License type: CC BY 4.0

Affiliation: Brigham and Women's Hospital, Harvard University

Abstract

Staphylococcus aureus generates and releases extracellular vesicles (EVs) that package cytosolic, cell-wall associated, and membrane proteins, as well as glycopolymers and exoproteins, including alpha hemolysin, leukocidins, phenol-soluble modulins, superantigens, and enzymes. S. aureus EVs, but not EVs from pore-forming toxin-deficient strains, were cytolytic for a variety of mammalian cell types, but EV internalization was not essential for cytotoxicity. Because S. aureus is subject to various environmental stresses during its encounters with the host during infection, we assessed how these exposures affected EV production in vitro. Staphylococci grown at 37 °C or 40 °C did not differ in EV production, but cultures incubated at 30 °C yielded more EVs when grown to the same optical density. S. aureus cultivated in the presence of oxidative stress, in iron-limited media, or with subinhibitory concentrations of ethanol, showed greater EV production as determined by protein yield and quantitative immunoblots. In contrast, hyperosmotic stress or subinhibitory concentrations of erythromycin reduced S. aureus EV yield. EVs represent a novel S. aureus secretory system that is affected by a variety of stress responses and allows the delivery of biologically active pore-forming toxins and other virulence determinants to host cells.

Highlights

IntroductionStaphylococcus aureus is a pathogenic bacterium that causes a wide spectrum of human diseases, ranging from mild skin lesions and surgical wound infections, to invasive and lifethreatening infections, such as pneumonia, osteomyelitis, endocarditis, and bacteremia [1]
Key Contribution: This study describes the diverse cargo contained within S. aureus extracellular vesicles, the unique biological activities associated with EVs, and the effect of different environmental stresses on EV production
Because S. aureus EVs can be endocytosed within host cells [27], EVs may serve as a novel secretory system for S. aureus to effectively transport toxins and other EV cargo to intracellular compartments

Summary

Introduction

Staphylococcus aureus is a pathogenic bacterium that causes a wide spectrum of human diseases, ranging from mild skin lesions and surgical wound infections, to invasive and lifethreatening infections, such as pneumonia, osteomyelitis, endocarditis, and bacteremia [1]. Many S. aureus isolates are resistant to commonly used antibiotics, and efforts to develop a vaccine for the prevention of staphylococcal infections have eluded success [2]. The pathogenesis of S. aureus infections is attributed to a wide array of virulence determinants that are associated with the cell surface, such as protein adhesins [3] and glycopolymers [4], or secreted to the environment, such as pore-forming toxins (PFTs) [5], superantigens [6], and proteases [7]

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