Mitochondria-Derived Vesicles Deliver Antimicrobial Reactive Oxygen Species to Control Phagosome-Localized Staphylococcus aureus, 2018,O'Riordan et al

[Andy]

Posting out of general interest

Highlights

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  Infection-induced ER stress stimulates macrophage mitochondrial peroxide production
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  MRSA infection triggers Parkin-dependent mitochondria-derived vesicle (MDV) generation
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  MDVs deliver the peroxide-generating enzyme Sod2 to bacteria-containing phagosomes
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  Mitochondrial Sod2 is required for peroxide accumulation in MRSA-containing phagosomes

Summary
Pathogenic bacteria taken up into the macrophage phagosome are the target of many anti-microbial mechanisms. Although mitochondria-derived antimicrobial effectors like reactive oxygen species (mROS) aid in bacterial killing, it is unclear how these effectors reach bacteria within the phagosomal lumen. We show here that endoplasmic reticulum stress triggered upon methicillin-resistant Staphylococcus aureus (MRSA) infection induces mROS that are delivered to bacteria-containing phagosomes via mitochondria-derived vesicles (MDVs). The endoplasmic reticulum stress sensor IRE1α induces mROS, specifically hydrogen peroxide (mH 2O 2), upon MRSA infection. MRSA infection also stimulates the generation of MDVs, which require the mitochondrial stress response factor Parkin, and contributes to mH 2O 2 accumulation in bacteria-containing phagosomes. Accumulation of phagosomal H 2O 2 requires Toll-like receptor signaling and the mitochondrial enzyme superoxide dismutase-2 (Sod2), which is delivered to phagosomes by MDVs. Sod2 depletion compromises mH 2O 2 production and bacterial killing. Thus, mitochondrial redox capacity enhances macrophage antimicrobial function by delivering mitochondria-derived effector molecules into bacteria-containing phagosomes.

Paywalled at https://www.cell.com/cell-host-microbe/pdfExtended/S1931-3128(18)30543-2

 

[lansbergen]

Thanks Andy.

I was looking for hydrogen peroxide because that can destroy the pathogen i suspect.

The higher the concentration the more toxic it becomes.

Anyone have any idea what symptoms can be expected from endogen produced high concentrations to destroy the pathogen?