scholarly journals Extracellular Vesicles and Their Role in Staphylococcus aureus Resistance and Virulence

2021 ◽  
Author(s):  
Brenda Silva Rosa da Luz ◽  
Vasco Azevedo ◽  
Yves Le-loir ◽  
Eric Guedon
Keyword(s):  
Staphylococcus Aureus ◽  
Veterinary Medicine ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Living Cells ◽  
Host Cells ◽  
Bacterial Survival ◽  
Extracellular Milieu ◽  
In Trans ◽  
Therapy Development

Staphylococcus aureus is a pathogen of great importance to clinical and veterinary medicine. Recently, there has been a growing interest in S. aureus extracellular vesicles (EVs) in the pathogenesis of this bacterium. Released by living cells into the extracellular milieu, EVs are membranous structures carrying macromolecules such as proteins, nucleic acids, and metabolites. These structures play several physiological roles and are, among others, considered a mechanism of intercellular communication within S. aureus populations but also in trans kingdom interactions. S. aureus EVs were shown to transport important bacterial survival and virulence factors, such as β-lactamases, toxins, and proteins associated with bacterial adherence to host cells, and to trigger the production of cytokines and promote tissue inflammation. In this chapter, we will review the main studies regarding S. aureus EVs, including their composition and roles in host-pathogen interactions, and the possible applications of EVs for vaccines and therapy development against staphylococcal infections.

scholarly journals Temperature Influences the Composition and Cytotoxicity of Extracellular Vesicles in Staphylococcus aureus

mSphere ◽  
2021 ◽  
Author(s):  
Paul Briaud ◽  
Andrew Frey ◽  
Emily C. Marino ◽  
Raeven A. Bastock ◽  
Riley E. Zielinski ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Nucleic Acids ◽  
Lipid Bilayer ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Host Cells ◽  
Content Type

Extracellular vesicles (EVs) are lipid bilayer spheres that contain proteins, nucleic acids, and lipids secreted by bacteria. They are involved in Staphylococcus aureus infections, as they package virulence factors and deliver their contents inside host cells.

scholarly journals Orchestration of human macrophage NLRP3 inflammasome activation by Staphylococcus aureus extracellular vesicles

2020 ◽  
Vol 117 (6) ◽  
pp. 3174-3184 ◽  
Author(s):  
Xiaogang Wang ◽  
William J. Eagen ◽  
Jean C. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Extracellular Vesicles ◽  
Biological Effects ◽  
Endocytic Pathway ◽  
Host Cells ◽  
Human Macrophage ◽  
Inflammasome Activation ◽  
Human Macrophages ◽  
Caspase 1 ◽  
Tlr2 Signaling

Release of extracellular vesicles (EVs) is a common feature among eukaryotes, archaea, and bacteria. However, the biogenesis and downstream biological effects of EVs released from gram-positive bacteria remain poorly characterized. Here, we report that EVs purified from a community-associated methicillin-resistant Staphylococcus aureus strain were internalized into human macrophages in vitro and that this process was blocked by inhibition of the dynamin-dependent endocytic pathway. Human macrophages responded to S. aureus EVs by TLR2 signaling and activation of NLRP3 inflammasomes through K+ efflux, leading to the recruitment of ASC and activation of caspase-1. Cleavage of pro–interleukin (IL)-1β, pro-IL-18, and gasdermin-D by activated caspase-1 resulted in the cellular release of the mature cytokines IL-1β and IL-18 and induction of pyroptosis. Consistent with this result, a dose-dependent cytokine response was detected in the extracellular fluids of mice challenged intraperitoneally with S. aureus EVs. Pore-forming toxins associated with S. aureus EVs were critical for NLRP3-dependent caspase-1 activation of human macrophages, but not for TLR2 signaling. In contrast, EV-associated lipoproteins not only mediated TLR2 signaling to initiate the priming step of NLRP3 activation but also modulated EV biogenesis and the toxin content of EVs, resulting in alterations in IL-1β, IL-18, and caspase-1 activity. Collectively, our study describes mechanisms by which S. aureus EVs induce inflammasome activation and reveals an unexpected role of staphylococcal lipoproteins in EV biogenesis. EVs may serve as a novel secretory pathway for S. aureus to transport protected cargo in a concentrated form to host cells during infections to modulate cellular functions.

scholarly journals Extracellular Vesicles Released by Leishmania: Impact on Disease Development and Immune System Cells

2021 ◽  
Author(s):  
Rogéria Cristina Zauli ◽  
Andrey Sladkevicius Vidal ◽  
Talita Vieira Dupin ◽  
Aline Correia Costa de Morais ◽  
Wagner Luiz Batista ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Immune Cells ◽  
Diagnostic Tool ◽  
Experimental Models ◽  
Host Cells ◽  
Disease Development ◽  
Leishmania Spp

Leishmania spp. release extracellular vesicles (EVs) containing parasite molecules, including several antigens and virulence factors. These EVs can interact with the host cells, such as immune cells, contributing to the parasite–host relationship. Studies have demonstrated that Leishmania-EVs can promote infection in experimental models and modulate the immune response. Although the immunomodulatory effect has been demonstrated, Leishmania-EVs can deliver parasite antigens and therefore have the potential for use as a new diagnostic tool and development of new therapeutic and vaccine approaches. This review aims to bring significant advances in the field of extracellular vesicles and Leishmania, focusing on their role in the cells of the immune system.

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

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 75
Author(s):  
Xiaogang Wang ◽  
Paul F. Koffi ◽  
Olivia F. English ◽  
Jean C. Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Extracellular Vesicles ◽  
Stress Responses ◽  
Cell Types ◽  
Biologically Active ◽  
Host Cells ◽  
Virulence Determinants ◽  
Subinhibitory Concentrations ◽  
Secretory System

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.

scholarly journals Pathogenic Delivery: The Biological Roles of Cryptococcal Extracellular Vesicles

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 754
Author(s):  
Haroldo C. de Oliveira ◽  
Rafael F. Castelli ◽  
Flavia C. G. Reis ◽  
Juliana Rizzo ◽  
Marcio L. Rodrigues
Keyword(s):  
Cryptococcus Neoformans ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Fungal Species ◽  
Host Cells ◽  
Host Interaction ◽  
Domains Of Life ◽  
Methods Of Isolation ◽  
Scientific Advances

Extracellular vesicles (EVs) are produced by all domains of life. In fungi, these structures were first described in Cryptococcus neoformans and, since then, they were characterized in several pathogenic and non-pathogenic fungal species. Cryptococcal EVs participate in the export of virulence factors that directly impact the Cryptococcus–host interaction. Our knowledge of the biogenesis and pathogenic roles of Cryptococcus EVs is still limited, but recent methodological and scientific advances have improved our understanding of how cryptococcal EVs participate in both physiological and pathogenic events. In this review, we will discuss the importance of cryptococcal EVs, including early historical studies suggesting their existence in Cryptococcus, their putative mechanisms of biogenesis, methods of isolation, and possible roles in the interaction with host cells.

scholarly journals The Role of hlb-Converting Bacteriophages in Staphylococcus aureus Host Adaption

2021 ◽  
pp. 1-14
Author(s):  
Carina Rohmer ◽  
Christiane Wolz
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Molecular Mechanisms ◽  
Opportunistic Pathogen ◽  
Bacterial Survival ◽  
Chronic Infections ◽  
Inhibitory Protein ◽  
Fitness Advantage ◽  
Genes Encoding ◽  
Life Threatening

As an opportunistic pathogen of humans and animals, <i>Staphylococcus aureus</i> asymptomatically colonizes the nasal cavity but is also a leading cause of life-threatening acute and chronic infections. The evolution of <i>S. aureus</i> resulting from short- and long-term adaptation to diverse hosts is tightly associated with mobile genetic elements<i>. S. aureus</i> strains can carry up to four temperate phages, many of which possess accessory genes encoding staphylococcal virulence factors. More than 90% of human nasal isolates of <i>S. aureus</i> have been shown to carry Sa3int phages, whereas invasive <i>S. aureus</i> isolates tend to lose these phages. Sa3int phages integrate as prophages into the bacterial <i>hlb</i> gene, disrupting the expression of the sphingomyelinase Hlb, an important virulence factor under specific infection conditions. Virulence factors encoded by genes carried by Sa3int phages include staphylokinase, enterotoxins, chemotaxis-inhibitory protein, and staphylococcal complement inhibitor, all of which are highly human specific and probably essential for bacterial survival in the human host. The transmission of <i>S. aureus</i> from humans to animals is strongly correlated with the loss of Sa3int phages, whereas phages are regained once a strain is transmitted from animals to humans. Thus, both the insertion and excision of prophages may confer a fitness advantage to this bacterium<i>.</i> There is also growing evidence that Sa3int phages may perform “active lysogeny,” a process during which prophages are temporally excised from the chromosome without forming intact phage particles. The molecular mechanisms controlling the peculiar life cycle of Sa3int phages remain largely unclear. Nevertheless, their regulation is likely fine-tuned to ensure bacterial survival within different hosts.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Xyloglucan processing machinery in Xanthomonas pathogens and its role in the transcriptional activation of virulence factors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Plinio S. Vieira ◽  
Isabela M. Bonfim ◽  
Evandro A. Araujo ◽  
Ricardo R. Melo ◽  
Augusto R. Lima ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Transcriptional Activation ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Citrus Canker ◽  
Effector Proteins ◽  
Glycoside Hydrolases ◽  
Host Cells ◽  
System A ◽  
Enzymatic Machinery

AbstractXyloglucans are highly substituted and recalcitrant polysaccharides found in the primary cell walls of vascular plants, acting as a barrier against pathogens. Here, we reveal that the diverse and economically relevant Xanthomonas bacteria are endowed with a xyloglucan depolymerization machinery that is linked to pathogenesis. Using the citrus canker pathogen as a model organism, we show that this system encompasses distinctive glycoside hydrolases, a modular xyloglucan acetylesterase and specific membrane transporters, demonstrating that plant-associated bacteria employ distinct molecular strategies from commensal gut bacteria to cope with xyloglucans. Notably, the sugars released by this system elicit the expression of several key virulence factors, including the type III secretion system, a membrane-embedded apparatus to deliver effector proteins into the host cells. Together, these findings shed light on the molecular mechanisms underpinning the intricate enzymatic machinery of Xanthomonas to depolymerize xyloglucans and uncover a role for this system in signaling pathways driving pathogenesis.

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