Variation among Staphylococcus aureus membrane vesicle proteomes affects cytotoxicity of host cells

Jeon, Hyejin; Oh, Man Hwan; Jun, So Hyun; Kim, Kyung Sik; Choi, Chi Won; Kwon, Hyo Il; Na, Seok Hyeon; Kim, Yoo Jeong; Nicholas, Asiimwe; Selasi, Gati Noble; Lee, Je Chul

doi:10.1016/j.micpath.2016.02.014

Cited by 74 publications

(92 citation statements)

References 36 publications

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“…In this study, however, MVs purified from a clinical S. aureus isolate from AD lesions are not cytotoxic to keratinocytes. Staphylococcus aureus 03ST17 MVs were not cytotoxic to HEp‐2 cells treated with up to 15 μg/mL . Instead, these extracellular vesicles elicit a pro‐inflammatory response in keratinocytes.…”

Section: Discussionmentioning

confidence: 88%

Staphylococcus aureus‐derived membrane vesicles exacerbate skin inflammation in atopic dermatitis

Jun

Lee

Kim

et al. 2016

Clin Experimental Allergy

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SummaryBackground Skin colonization or infection with Staphylococcus aureus is known to trigger aggravation of atopic dermatitis (AD). However, the exact mechanisms by which S. aureus can worsen AD are unknown. Objective We investigated whether and how S. aureus-derived membrane vesicles (MVs) contribute to worsening of AD. Methods Immunohistochemical and immunoelectron microscopic analyses were performed to detect staphylococcal protein A (SPA) in the epidermis of AD lesions. HaCaT cells were treated with S. aureus MVs and were analysed for the expression of cytokine genes. Immunopathology and cytokine gene profiles were analysed after topical application of S. aureus MVs to AD-like skin lesions in a mouse model. Results The MV component SPA was detected in the keratinocytes as well as in the intercellular space of the epidermis of AD lesions colonized with S. aureus. Intact MVs from S. aureus delivered their components to keratinocytes and stimulated pro-inflammatory cytokine gene expression in vitro. A knock-down of Toll-like receptor 2 or nucleotidebinding oligomerization domain 2 using small interfering RNAs suppressed interleukin-8 gene expression. Topical application of intact S. aureus MVs to AD-like skin lesions in the mouse model induced massive infiltration of inflammatory cells and the resulting eczematous dermatitis. This inflammatory reaction was associated with a mixed Th1/Th2 immune response and enhanced expression of chemokine genes in AD-like skin lesions. Conclusions and Clinical Relevance This study showed the importance of S. aureus MVs as a potent mediator for worsening of AD among many exogenous worsening factors of AD. Thus, S. aureus MVs may be regarded as one of the therapeutic targets for the management of AD aggravation.

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Section: Discussionmentioning

confidence: 88%

Staphylococcus aureus‐derived membrane vesicles exacerbate skin inflammation in atopic dermatitis

Jun

Lee

Kim

et al. 2016

Clin Experimental Allergy

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“…EV formation by at least 10 different S. aureus strains has been reported 16,17,28,32 , and EV shedding is likely common to many clinical isolates. We isolated and characterized EVs from USA300 strain JE2, representing the major clone associated with CA-MRSA disease in the U.S 33 .…”

Section: Resultsmentioning

confidence: 99%

“…More recent work has described the production and release of extracellular vesicles (EVs) from Gram positive bacteria, such as S. aureu 16,17 , Streptococcus pneumoniae 7 , and Bacillus anthracis 6 . Only actively metabolizing bacteria generate EVs, and EVs are not released by killed cells 9 .…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, EVs isolated from S. pneumoniae protected mice against lethal pneumonia 7 . Despite the documented immunogenicity and protective efficacy of bacterial EV-based vaccines, EV preparations derived from some bacterial pathogens may contain toxins or other virulence factors that potentially damage host cells 17,28-31 . The development of EVs as a vaccine platform will require a more thorough characterization of the mechanisms of EV biogenesis to allow for consistent production with adequate quality assurance.…”

Section: Introductionmentioning

confidence: 99%

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The biogenesis of extracellular vesicles fromStaphylococcus aureusand their application as a novel vaccine platform

Wang

Weidenmaier

Lee

2018

Preprint

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31Gram-positive bacteria secrete extracellular vesicles (EVs) that package diverse bacterial 32 antigens and play key roles in bacterial pathogenesis. However, the mechanisms underlying EV 33 production in Gram-positive bacteria are poorly understood. We purified and characterized EVs 34 from a community-associated methicillin-resistant Staphylococcus aureus isolate (USA300) and 35 investigated mechanisms underlying EV production. Native EVs contained 165 proteins, including 36 cytosolic, surface, and secreted proteins, autolysins, and numerous cytolysins. Staphylococcal 37 alpha-type phenol-soluble modulins (surfactant-like peptides) promoted EV biogenesis, 38presumably by acting at the cytoplasmic membrane, whereas peptidoglycan crosslinking and 39 autolysin activity were found to increase EV production by altering the permeability of the 40 staphylococcal cell wall. To address the immunogenicity of EVs, we created engineered EVs 41 (eng-EVs) by expressing detoxified proteins HlaH35L and LukE in EVs generated from a nontoxic 42 S. aureus ∆agr∆spa mutant. Eng-EVs exhibited no cytotoxicity in vitro, and mice immunized with 43 the eng-EVs produced toxin-neutralizing antibodies and showed reduced lethality in a mouse 44 sepsis model. Our study reveals novel mechanisms underlying S. aureus EV production and 45 highlights the usefulness of EVs as a novel S. aureus vaccine platform. 46 47 peer-reviewed)

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“…Clostridium difficile, Porphyromonas gingivalis, Neisseria meningitidis and Staphylococcus aureus have displayed immunological outcomes, including those mediated by TLR2 and TLR4 [1][2][3][4][5]. Moreover, in vitro transcriptome analysis suggested that LPS structural changes can be used to alter immunological outcome [6].…”

Section: Mvs Isolated From Diverse Species Such As Legionella Pneumomentioning

confidence: 99%

Bacterial Membrane Vesicles: New Therapeutic Prospectives

Giagulli¹

2018

acta scient microb

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Novel recombinant MV vaccines, though in the early stages of development, represent a great promise for the future to combat different diseases. This approach may be more appropriate for antigens that require surface presentation to retain their native immunogenic conformation, but is limited to small proteins or pep- At present, even if the development of bacterial MVs as a new therapeutic prospective looks promising, MV research is still at the beginning and some issues need to be addressed before their use as therapeutic agents. In particular, verification of the specificity of MV delivery is needed to rule out toxic side effects into non-target tissues.

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Variation among Staphylococcus aureus membrane vesicle proteomes affects cytotoxicity of host cells

Cited by 74 publications

References 36 publications

Staphylococcus aureus‐derived membrane vesicles exacerbate skin inflammation in atopic dermatitis

Staphylococcus aureus‐derived membrane vesicles exacerbate skin inflammation in atopic dermatitis

The biogenesis of extracellular vesicles fromStaphylococcus aureusand their application as a novel vaccine platform

Bacterial Membrane Vesicles: New Therapeutic Prospectives

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