Flavodoxin-Like Proteins Protect from Oxidative Stress and Promote Virulence

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Oxidative damage is a fundamental problem for cells and a particular challenge for microbial pathogens, which require special mechanisms to resist the oxidative attack by the host immune system. We identified four proteins in the human fungal pathogen Candida albicans that belong to a large family of enzymes in bacteria and plants that reduce quinone molecules to detoxify them. Interestingly, mutational studies in C. albicans showed that these enzymes also confer resistance to a wide range of oxidants, suggesting they may have broader impact by reducing the major quinone present in cells (ubiquinone or coenzyme Q). In support of this, we found that mutating the COQ3 gene to block ubiquinone synthesis rendered cells highly sensitive to oxidative stress, revealing that it plays a very important antioxidant function in addition to its well known role in energy metabolism. These quinone reductases play a critical role in vivo, as they were required for virulence in mouse infections studies. Since mammalian cells lack this type of quinone reductase, this difference could be exploited to develop much needed novel therapeutic approaches for fungal and bacterial pathogens.

Vyšlo v časopise: Flavodoxin-Like Proteins Protect from Oxidative Stress and Promote Virulence. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005147
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005147

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