Candida albicans Induces Arginine Biosynthetic Genes in Response to Host-Derived Reactive Oxygen Species

Department of Microbiology and Molecular Genetics, University of Texas Health Science Center at Houston.
Eukaryotic Cell (Impact Factor: 3.18). 11/2012; 12(1). DOI: 10.1128/EC.00290-12
Source: PubMed


The interaction of Candida albicans with phagoctyes of the host's innate immune system is highly dynamic, the outcome of which directly impacts the progression of infection. While the switch to hyphal growth within the macrophage is the most obvious physiological response, much of the genetic response reflects nutrient starvation - translational repression and induction of alternative carbon metabolism. Changes in amino acid metabolism are not seen, with the striking exception of arginine biosynthesis, which is upregulated in its entirety during co-culture with macrophages. Using single cell reporters, we show here that arginine biosynthetic genes are induced specifically in phagocytosed cells. This induction is lower in magnitude than during arginine starvation in vitro, and is not driven by an arginine deficiency within the phagocyte but instead by exposure to reactive oxygen species. Curiously, these genes are induced in a narrow window of sublethal ROS concentrations. C. albicans cells phagocytosed by primary macrophages deficient in the gp91(phox) subunit of the phagocyte oxidase do not express the ARG pathway, indicating that the induction is dependent on the phagocyte oxidative burst. C. albicans arg pathway mutants are retarded in germ-tube and hyphal formation within macrophages, but are not notably more sensitive to ROS. We also find that the ARG pathway is not regulated by the general amino acid control response, but by transcriptional regulators similar to the Saccharomyces cerevisiae ArgR complex. In summary, phagocytosis induces this single amino acid biosynthetic pathway in an ROS-dependent manner.

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Available from: Robert T Wheeler, Jun 20, 2014
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    • "Bone marrow-derived macrophages (BMDMs) were isolated from sacrificed ICR mice as described previously [23] and cultured at 37°C with 5% CO2 in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% FBS, Pen-Strep, and 10 ng/mL mouse granulocyte-macrophage colony-stimulating factor (GM-CSF). All animal work was performed in accordance with protocols approved by the Animal Welfare Committee of the University of Texas Health Science Center at Houston. "
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