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

Abstract

Candida albicans is a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that the C. albicans genome encodes 6 orthologues of the Saccharomyces. cerevisiae general amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show that C. albicans Gap2 is the functional orthologue of ScGap1 and that C. albicans Gap4 is an orthologue of ScSam3, an S-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor of C. albicans.

Methionine is required for cAMP‐PKA‐mediated morphogenesis and virulence of Candida albicans

“…Therefore, we tested whether addition of methionine metabolites could also induce morphogenesis in minimal low glucose conditions and, if so, whether this requires the high affinity permease Mup1. SAM is one of the most important molecules that are generated from methionine, and we have previously characterized Gap4 as a specific SAM transporter required for SAM‐induced morphogenesis (Kraidlova et al ., ). Hence, as expected, addition of 100 µM SAM triggered morphogenesis in both wild‐type and mup1/mup1 strains (Fig.…”

“…Possibly, upon uptake, there is a higher percentage of methionine that is converted to SAM, causing more decarboxylation and subsequent polyamine biosynthesis, ultimately leading to morphogenesis. We showed, however, that other permeases known to take up methionine, such as some of the general amino acid permeases (Gaps), namely Gap1, Gap2 and Gap6 (Kraidlova et al ., ), do not have an effect on methionine‐induced morphogenesis (Kraidlova et al ., ).…”

“…Deletion results in a significant reduction in the blood stage of parasites as well as a strong defect in mosquito transmission (Hart et al, 2016). Furthermore, SAM transporters are present in only a few organisms and next to S. cerevisiae and C. albicans, trypanosomids are amongst them, which might be related to their function in pathogenesis (Thomas and Surdin-Kerjan, 1997;Goldberg et al, 1999;Dridi et al, 2010;Kraidlova et al, 2016).…”

“…However, it is unclear, whether the yeast-to-hyphae switch is directly driven by the extracellular sensing of amino acids through Csy1 or whether morphogenesis is the consequence of amino acid transport by SPS-regulated permeases. A subset of these permeases includes six general amino acid permeases (Gaps), which represent orthologues of the S. cerevisiae general amino acid permease Gap1 (Kraidlova et al, 2016).…”

CO2enhances the ability ofCandida albicansto form biofilms, overcome nutritional immunity and resist antifungal treatment

“…Likewise, significantly differentially expressed genes possessing the GO term ‘amino acid transport’ were primarily upregulated (Figure 6B). The most highly upregulated of these was GAP2 which encodes a general amino acid permease 57 . GAP2 was in fact the highest upregulated gene of the entire RNA-Seq data set with a 4.60 log2 fold change.…”