RT info:eu-repo/semantics/article
T1 Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi
A1 Mourenza Flórez, Álvaro
A1 Bravo-Santano, Natalia
A1 Pradal, Inés
A1 Gil Santos, José Antonio
A1 Mateos Delgado, Luis Mariano
A1 Letek, Michal
A2 Microbiologia
K1 Biología
K1 Rhodococcus equi
K1 Intracellular pathogen
K1 Mycoredoxins
K1 Virulence
K1 Macrophages
AB [EN] 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
PB MDPI
LK http://hdl.handle.net/10612/15050
UL http://hdl.handle.net/10612/15050
NO Mourenza, Á., Bravo-Santano, N., Pradal, I., Gil, J. A., Mateos, L. M., & Letek, M. (2019). Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi. Antioxidants, 8(11), 558. MDPI AG. Retrieved from http://dx.doi.org/10.3390/antiox8110558
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 19-may-2024