The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from Staphylococcus aureus

Schlatterer, Katja; Beck, Christian; Hanzelmann, Dennis; Lebtig, Marco; Fehrenbacher, Birgit; Schaller, Martin; Ebner, Patrick; Nega, Mulugeta; Otto, Michael; Kretschmer, Dorothee; Peschel, Andreas

doi:10.1128/mbio.01851-18

Cited by 73 publications

(112 citation statements)

References 39 publications

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“…Morphologically, MVs of average smaller diameter were distributed to the lower density fractions (F1–F3), in contrast to higher density fractions (F4–F6) where larger sized MVs were observed. Consistent with previous data regarding S. aureus MVs 25 , 33 , 40 – 44 , our size distribution analysis of the pooled MV fractions F1–F3 showed a size distribution range from ~ 20 to ~ 300 nm in diameter (Fig. 1 D), with an average diameter of 68.5 nm.…”

Section: Resultssupporting

confidence: 92%

Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

Rodriguez

Kuehn

2020

Sci Rep

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Bacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such as Staphylococcus aureus and their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells. S. aureus produce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show that S. aureus secretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses.

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Section: Resultssupporting

confidence: 92%

Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

Rodriguez

Kuehn

2020

Sci Rep

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“…Like with OMVs, changes in plasma membrane homeostasis can modulate the release of BMVs. Increased membrane fluidity in S. aureus when high levels of phenol-soluble modulin are present, increased the release of BMVs [101]. Similarly, antibiotics are known to promote BMV release by cross-linking plasma membrane peptidoglycans [102].…”

Section: Bacteria-derived Evsmentioning

confidence: 99%

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development

Macia

Nanan

Hosseini‐Beheshti

et al. 2019

IJMS

151

141

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Extracellular vesicles (EVs) are blebs of either plasma membrane or intracellular membranes carrying a cargo of proteins, nucleic acids, and lipids. EVs are produced by eukaryotic cells both under physiological and pathological conditions. Genetic and environmental factors (diet, stress, etc.) affecting EV cargo, regulating EV release, and consequences on immunity will be covered. EVs are found in virtually all body fluids such as plasma, saliva, amniotic fluid, and breast milk, suggesting key roles in immune development and function at different life stages from in utero to aging. These will be reviewed here. Under pathological conditions, plasma EV levels are increased and exacerbate immune activation and inflammatory reaction. Sources of EV, cells targeted, and consequences on immune function and disease development will be discussed. Both pathogenic and commensal bacteria release EV, which are classified as outer membrane vesicles when released by Gram-negative bacteria or as membrane vesicles when released by Gram-positive bacteria. Bacteria derived EVs can affect host immunity with pathogenic bacteria derived EVs having pro-inflammatory effects of host immune cells while probiotic derived EVs mostly shape the immune response towards tolerance.

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“…PSMs have been implicated in a variety of staphylococcal processes (reviewed in Peschel & Otto, 2013;Otto, 2014). Amongst others, PSMs are involved in formation of staphylococcal biofilms (Le, Dastgheyb, Ho, & Otto, 2014;Periasamy et al, 2012) and amyloid structures, contribute to nonclassical protein secretion (Ebner et al, 2017) and release of TLR2-activating lipoproteins via extracellular vesicles (Hanzelmann et al, 2016;Schlatterer et al, 2018).…”

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confidence: 99%

In or out: Phagosomal escape ofStaphylococcus aureus

Moldovan

Fraunholz

2019

Cellular Microbiology

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Staphylococcus aureus is internalised by host cells in vivo, and recent research results suggest that the bacteria use this intracellularity to persist in the host and form a reservoir for recurrent infections. However, in different cells types, the pathogen resorts to alternative strategies to survive phagocytosis and the antimicrobial mechanisms of host cells. In non‐professional phagocytes, S. aureus either escapes the endosome followed by cytoplasmic replication or replicates within autophagosomes. Professional phagocytes possess a limited capacity to kill S. aureus and hence the bacteria, well equipped with immune evasive mechanisms, replicate within the cells, eventually lyse out of the cells and thus persist in a continuous cycle of phagocytosis, host cell death, and bacterial release.

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The Mechanism behind Bacterial Lipoprotein Release: Phenol-Soluble Modulins Mediate Toll-Like Receptor 2 Activation via Extracellular Vesicle Release from Staphylococcus aureus

Cited by 73 publications

References 39 publications

Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development

In or out: Phagosomal escape ofStaphylococcus aureus

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