학술논문

Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi .
Document Type
Academic Journal
Author
Mourenza Á; Department of Molecular Biology, Area of Microbiology, University of León, 24071 León, Spain.; Bravo-Santano N; Health Sciences Research Centre, University of Roehampton, London SW15 4JD, UK.; Pradal I; Department of Molecular Biology, Area of Microbiology, University of León, 24071 León, Spain.; Gil JA; Department of Molecular Biology, Area of Microbiology, University of León, 24071 León, Spain.; Mateos LM; Department of Molecular Biology, Area of Microbiology, University of León, 24071 León, Spain.; Letek M; Health Sciences Research Centre, University of Roehampton, London SW15 4JD, UK.
Source
Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101668981 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3921 (Print) Linking ISSN: 20763921 NLM ISO Abbreviation: Antioxidants (Basel) Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2076-3921
Abstract
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 identified three mycoredoxin-encoding genes ( mrx ) in the genome of R. equi , and we investigated their role in virulence. Importantly, the intracellular survival of a triple mrx -null mutant ( Δmrx1Δmrx2Δmrx3 ) in murine macrophages was fully impaired. However, each mycoredoxin alone could restore the intracellular proliferation rate of R. equi Δmrx1Δmrx2Δmrx3 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 R. equi 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 R. equi to different oxidative stressors. Interestingly, all mrx genes did have overlapping roles in the resistance to sodium hypochlorite. In contrast, only mrx1 was essential for the survival against high concentrations of nitric oxide, while mrx3 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 R. equi and, therefore, these proteins may be considered interesting targets for the development of new anti-infectives.