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

Article (PDF Available)inEukaryotic Cell 12(1) · November 2012with43 Reads
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.