Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi
is a facultative intracellular pathogen that can survive within macrophages of a wide variety of hosts, including immunosuppressed humans. Current antibiotherapy is often ineffective, and novel therapeutic strategies are urgently needed to tackle infections caused by this pathogen. In this study, we...
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Veröffentlicht in: | Antioxidants 2019-11, Vol.8 (11), p.558 |
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Sprache: | eng |
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Zusammenfassung: | is a facultative intracellular pathogen that can survive within macrophages of a wide variety of hosts, including immunosuppressed humans. Current antibiotherapy is often ineffective, and novel therapeutic strategies are urgently needed to tackle infections caused by this pathogen. In this study, we identified three mycoredoxin-encoding genes (
) in the genome of
, and we investigated their role in virulence. Importantly, the intracellular survival of a triple
-null mutant (
) in murine macrophages was fully impaired. However, each mycoredoxin alone could restore the intracellular proliferation rate of
to wild type levels, suggesting that these proteins could have overlapping functions during host cell infection. Experiments with the reduction-oxidation sensitive green fluorescent protein 2 (roGFP2) biosensor confirmed that
was exposed to redox stress during phagocytosis, and mycoredoxins were involved in preserving the redox homeostasis of the pathogen. Thus, we studied the importance of each mycoredoxin for the resistance of
to different oxidative stressors. Interestingly, all
genes did have overlapping roles in the resistance to sodium hypochlorite. In contrast, only
was essential for the survival against high concentrations of nitric oxide, while
was not required for the resistance to hydrogen peroxide. Our results suggest that all mycoredoxins have important roles in redox homeostasis, contributing to the pathogenesis of
and, therefore, these proteins may be considered interesting targets for the development of new anti-infectives. |
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ISSN: | 2076-3921 2076-3921 |
DOI: | 10.3390/antiox8110558 |