Flavodoxin-Like Proteins Protect Candida albicans from Oxidative Stress and Promote Virulence

PLoS Pathogens
Lifang LiJames B Konopka

Abstract

The fungal pathogen Candida albicans causes lethal systemic infections in humans. To better define how pathogens resist oxidative attack by the immune system, we examined a family of four Flavodoxin-Like Proteins (FLPs) in C. albicans. In agreement with previous studies showing that FLPs in bacteria and plants act as NAD(P)H quinone oxidoreductases, a C. albicans quadruple mutant lacking all four FLPs (pst1Δ, pst2Δ, pst3Δ, ycp4Δ) was more sensitive to benzoquinone. Interestingly, the quadruple mutant was also more sensitive to a variety of oxidants. Quinone reductase activity confers important antioxidant effects because resistance to oxidation was restored in the quadruple mutant by expressing either Escherichia coli wrbA or mammalian NQO1, two distinct types of quinone reductases. FLPs were detected at the plasma membrane in C. albicans, and the quadruple mutant was more sensitive to linolenic acid, a polyunsaturated fatty acid that can auto-oxidize and promote lipid peroxidation. These observations suggested that FLPs reduce ubiquinone (coenzyme Q), enabling it to serve as an antioxidant in the membrane. In support of this, a C. albicans coq3Δ mutant that fails to synthesize ubiquinone was also highly sensitive to oxidative ...Continue Reading

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Citations

Mar 25, 2016·Molecular Biology of the Cell·Hong X WangJames B Konopka
Jan 12, 2019·PLoS Genetics·Lois M Douglas, James B Konopka
Jul 28, 2019·Biomolecules·Jakub Zahumensky, Jan Malinsky
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Feb 28, 2016·The Journal of Microbiology·Lois M Douglas, James B Konopka
May 15, 2019·International Journal of Molecular Sciences·Mónica GalochaMiguel C Teixeira
Dec 7, 2019·The Journal of Biological Chemistry·Sabrina S SchatzmanValeria C Culotta
Sep 18, 2020·Microbiology and Molecular Biology Reviews : MMBR·Carla E LanzeJames B Konopka
Nov 30, 2016·Frontiers in Cellular and Infection Microbiology·Caroline M MarcosAna M Fusco-Almeida
Jul 1, 2020·BioMed Research International·Yunierkis Perez-CastilloDamião P de Sousa
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Jan 27, 2018·Journal of Fungi·Jenna E FoderaroJames B Konopka
Mar 22, 2019·Journal of Natural Products·Jana BraeselAlessandra S Eustáquio

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Methods Mentioned

BETA
fluorescence microscopy
PCR
restriction

Software Mentioned

Zeiss AxioVision
Clustal W
SAT Flipper
GraphPad
Prism

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