The pathogenic yeast Candida parapsilosis degrades various hydroxy derivatives of benzenes and benzoates by the gentisate and 3-oxoadipate pathways. We identified the genes MNX1, MNX2, MNX3, GDX1, HDX1 and FPH1 that code for enzymes involved in these pathways in the complete genome sequence of C. parapsilosis. Next, we demonstrated that MNX1, MNX2, MNX3 and GDX1 are inducible and transcriptionally controlled by hydroxyaromatic substrates present in cultivation media. Our results indicate that MNX1 and MNX2 code for flavoprotein monooxygenases catalysing the first steps in the 3-oxoadipate and gentisate pathways, respectively (i.e. 4-hydroxybenzoate 1-hydroxylase and 3-hydroxybenzoate 6-hydroxylase). Moreover, we found that the two pathways differ by their intracellular localization. The enzymes of the 3-oxoadipate pathway, Mnx1p and Mnx3p, localize predominantly in the cytosol. In contrast, intracellular localization of the components of the gentisate pathway, Mnx2p and Gdx1p, depends on the substrate in the cultivation medium. In cells growing on glucose these proteins localize in the cytosol, whereas in media containing hydroxyaromatic compounds they associate with mitochondria. Finally, we showed that the overexpression of MNX1 or MNX2 increases the tolerance of C. parapsilosis cells to the antifungal drug terbinafine.

The yeast Candida parapsilosis is an opportunistic human pathogen frequently associated with nosocomial infections in neonates and patients with diminished immunity. A growing number of studies powered by recent advances in molecular genetics and genomics provide a background for uncovering the molecular basis of its virulence that suggests promising avenues for therapeutic intervention against this pathogen. Importantly, these studies also revealed several unique genetic and physiological features absent in model organisms, such as baker's and fission yeasts. Hence, besides the clinical impact, C. parapsilosis represents an interesting non-conventional model suitable for investigations of several fundamental biological phenomena in cellular physiology, morphogenesis, and genome maintenance. In this study, we provide a concise review on C. parapsilosis biology and highlight its interesting biological features. In addition, we summarize approaches for genetic manipulation, which have enhanced research on this species by overcoming limitations of conventional genetic analysis caused primarily by an apparent absence of a sexual cycle and the diploid state of its genome.