Systemic candidiasis impacts upon iron homeostasis of both the fungus and the host.

<p><b>Panels A</b> and <b>B,</b> disturbed host iron homeostasis affects iron acquisition strategies of <i>C. albicans</i>. Fungal cells from either early (panel <b>A</b>, smaller inset) or advanced (panel <b>A</b>, larger image) stages of infection were dissected via laser capture microscopy, RNA was extracted, amplified, and abundances of the specific transcripts assessed by qRT-PCR (panel <b>B</b>). The expression of genes from the three major <i>C. albicans</i> iron acquisition pathways was assessed: (1) xenosiderophore acquisition – <i>SIT1</i> (orf19.2179) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003676#ppat.1003676-Heymann1" target="_blank">[42]</a> (no signal, not shown); (2) reductive iron acquisition – <i>ALS3</i> (orf19.1816), <i>FTR1</i> (orf19.7219) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003676#ppat.1003676-Knight1" target="_blank">[43]</a>; (3) haem-iron acquisition –<i>CSA1</i> (orf19.7114), <i>CSA2</i> (orf19.3117), <i>PGA10</i> (orf19.5674), and <i>HMX1</i> (orf19.6073) <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003676#ppat.1003676-Almeida1" target="_blank">[14]</a>. The differences in gene expression patterns between the centre and rim of advanced lesions probably reflect population heterogeneity within fungal lesions <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003676#ppat.1003676-Barelle1" target="_blank">[53]</a>, with the cells in the centre tightly knit and in contact with each other rather than the host, and not as metabolically active as the cells from the rim exposed to the host tissue. (<b>B</b>). The data presented are normalised to <i>ACT1</i> expression and represent means from at least three independent biological (lesion material) replicates. Greyed gene names, no transcript detection; error bars, standard deviations from the mean. Normalised transcript abundances were compared to the ‘early’ sample, differences were considered statistically significant (asterisks) for p≤0.05 in two-tailed t-test using Mann-Whitney U statistics. In panel <b>A</b>, the size bars correspond to 100 µm. <b>Panel C</b>, the effect of systemic candidiasis on the iron homeostasis of the host. During advanced candidiasis, the splenic red blood cell recycling function is perturbed presumably due to active clearance of fungal infection from that organ, while the renal involvement in host iron homeostasis increases. Blue colour intensity represents the renal iron distribution and relative concentration in the tissue, with <i>C. albicans</i> lesions represented by purple circles. See text for details.