Neutrophil-generated HOCl leads to non-specific thiol oxidation in phagocytized bacteria.
Elife
; 72018 03 06.
Article
en En
| MEDLINE
| ID: mdl-29506649
ABSTRACT
Phagocytic immune cells kill pathogens in the phagolysosomal compartment with a cocktail of antimicrobial agents. Chief among them are reactive species produced in the so-called oxidative burst. Here, we show that bacteria exposed to a neutrophil-like cell line experience a rapid and massive oxidation of cytosolic thiols. Using roGFP2-based fusion probes, we could show that this massive breakdown of the thiol redox homeostasis was dependent on phagocytosis, presence of NADPH oxidase and ultimately myeloperoxidase. Interestingly, the redox-mediated fluorescence change in bacteria expressing a glutathione-specific Grx1-roGFP2 fusion protein or an unfused roGFP2 showed highly similar reaction kinetics to the ones observed with roGFP2-Orp1, under all conditions tested. We recently observed such an indiscriminate oxidation of roGFP2-based fusion probes by HOCl with fast kinetics in vitro. In line with these observations, abating HOCl production in immune cells with a myeloperoxidase inhibitor significantly attenuated the oxidation of all three probes in bacteria.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Compuestos de Sulfhidrilo
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Ácido Hipocloroso
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Escherichia coli
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Antibacterianos
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Neutrófilos
Idioma:
En
Revista:
Elife
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania