Roles of Different Peptide Transporters in Nutrient Acquisition in Candida albicans

Abstract

Fungi possess two distinct proton-coupled peptide transport systems, the dipeptide/tripeptide transporters (PTR) and the oligopeptide transporters (OPT), which enable them to utilize peptides as nutrients. In the pathogenic yeast Candida albicans, peptide transporters are encoded by gene families consisting of two PTR genes and eight OPT genes. To gain insight into the functions and importance of specific peptide transporters, we generated mutants lacking the two dipeptide/tripeptide transporters Ptr2 and Ptr22, as well as the five major oligopeptide transporters Opt1 to Opt5. These mutants were unable to grow in media containing peptides as the sole nitrogen source. Forced expression of individual peptide transporters in the septuple mutants showed that Ptr2 and Ptr22 could utilize all tested dipeptides as substrates but differed in their abilities to transport specific tripeptides. Interestingly, several oligopeptide transporters, which are thought to transport peptides consisting of more than three amino acids, also mediated the uptake of tripeptides. Opt1 especially turned out to be a highly flexible transporter that enabled growth on all tripeptides tested and could even utilize a dipeptide, a function that has never been ascribed to this family of peptide transporters. Despite their inability to grow on proteins or peptides, the opt1⌬ opt2⌬ opt3⌬ opt4⌬ opt5⌬ ptr2⌬ ptr22⌬ septuple mutants had no in vivo fitness defect in a mouse model of gastrointestinal colonization. Therefore, the nutritional versatility of C. albicans enables it to utilize alternative nitrogen sources in this host niche, which probably contributes to its success as a commensal and pathogen in mammalian hosts.

Characterization of the Candida albicans Amino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is an S -Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis

“…Under both conditions, the cells must be able to sense and take up the available nutrients present in a specific niche. To allow the uptake of amino acids, C. albicans cells secrete a large number of hydrolase enzymes (mainly belonging to the secreted aspartyl proteinase gene family) that convert proteins into peptides and amino acids that can be taken up by peptide transporters or amino acid permeases, respectively (26, 43). Previously, it was shown that the capacity to take up amino acids is strongly linked with virulence.…”

Candida Survival Strategies

“…In addition to the reprogramming of metabolism in response to starvation, C. albicans possesses various transport mechanisms for peptides, amino acids, etc. that can be upregulated to acquire nutrients from degraded complex host molecules (Dunkel et al, 2013;Kraidlova, Van Zeebroeck, Van Dijck, & Sychrova, 2011;Ramachandra et al, 2014). The impact of metabolism upon Candida pathogenicity has recently been reviewed in detail (Brown, Budge, et al, 2014;Ene & Brown, 2014); thus we will only shortly summarize the current knowledge.…”

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).…”