Dur3 is the major urea transporter in Candida albicans and is co-regulated with the urea amidolyase Dur1,2

Abstract

Hemiascomycetes, including the pathogen Candida albicans, acquire nitrogen from urea using the urea amidolyase Dur1,2, whereas all other higher fungi use primarily the nickel-containing urease. Urea metabolism via Dur1,2 is important for resistance to innate host immunity in C. albicans infections. To further characterize urea metabolism in C. albicans we examined the function of seven putative urea transporters. Gene disruption established that Dur3, encoded by orf 19.781, is the predominant transporter. [14C]Urea uptake was energy-dependent and decreased approximately sevenfold in a dur3Δ mutant. DUR1,2 and DUR3 expression was strongly induced by urea, whereas the other putative transporter genes were induced less than twofold. Immediate induction of DUR3 by urea was independent of its metabolism via Dur1,2, but further slow induction of DUR3 required the Dur1,2 pathway. We investigated the role of the GATA transcription factors Gat1 and Gln3 in DUR1,2 and DUR3 expression. Urea induction of DUR1,2 was reduced in a gat1Δ mutant, strongly reduced in a gln3Δ mutant, and abolished in a gat1Δ gln3Δ double mutant. In contrast, DUR3 induction by urea was preserved in both single mutants but reduced in the double mutant, suggesting that additional signalling mechanisms regulate DUR3 expression. These results establish Dur3 as the major urea transporter in C. albicans and provide additional insights into the control of urea utilization by this pathogen.

Histatin 5 Uptake by Candida albicans Utilizes Polyamine Transporters Dur3 and Dur31 Proteins

“…Therefore, it is expected that these permeases have a role in virulence. Interestingly, the Dur3 deletion mutant was not attenuated in systemic virulence (45). However, our results found that although deletion of DUR3 reduced spermidine uptake by half, deletion of both DUR3 and DUR31 was required for the most extensive reduction in spermidine transport.…”

“…Bensen et al (43) first referred to C. albicans orf19.6656 as DUR3, and it became the standard name. Later Braun et al (44) and Navarathna et al (45) referred to C. albicans orf19.781 (as well as orf19.6656) as DUR3. Our homology analyses illustrate the pitfalls in the existing nomenclature.…”

“…The alignment of amino acid sequences of orf19.6656 and orf19.781 showed only 16% amino acid sequence identities, which confirms that orf19.6656 and orf19.781 each code for two significantly different proteins. Thus, we propose designating C. albicans orf19.781 as Dur3 because it is the true ortholog of the S. cerevisiae Dur3 protein and is a major inducible urea trans-porter (45), and designating C. albicans orf19.6656 as Dur31. Our analysis clearly shows Dur1,2 is not part of the Dur membrane transporter family but instead are intracellular enzymes involved in the Degradation of urea (hence the DUR nomenclature).…”

The Biotrophic Development of Ustilago maydis Studied by RNA-Seq Analysis

“…The top five induced transporters were two putative urea permeases dur3-1 (UMAG_02625) and dur3-2 (UMAG_06253), two putative oligopeptide transporters (OPT) opt2 (UMAG_11057) and opt4 (UMAG_02387), and the candidate methylammonium permease (MEP) ump2 (UMAG_05889) (Supplemental Data Set 11, Figures 4A and 4D). In fungi, related transporter families are required for nitrogen utilization from peptides, urea and ammonium, respectively (ElBerry et al, 1993;Lorenz and Heitman, 1998;Hauser et al, 2001;Abreu et al, 2010;Hartmann et al, 2011;Navarathna et al, 2011;Dunkel et al, 2013), while OPTs can also mediate sulfur utilization by taking up glutathione (Bourbouloux et al, 2000). All five transporters are located in the magenta expression module ( Figure 2C), and are thus linked to biotrophy (Supplemental Data Set 11).…”

Enhancement of urea uptake in Chinese rice wine yeast strain N85 by the constitutive expression ofDUR3for ethyl carbamate elimination

“…In addition to transporting urea into yeast cells, it also facilitates the uptake of polyamines and regulates intracellular boron concentrations (16,17). However, the existence of preponderant nitrogen, such as polyamines, would repress the expression of urea permease (6,17,18).…”