C. albicans requires high capacity amino acid uptake for
virulent growth.
Paula Martínez, Per O. Ljungdahl
Yeast Molecular Biology, Ludwig Inst. Cancer Research, Box 240,
Stockholm, 171 77, Sweden (pmar@licr.ki.se)
The C. albicans genome encodes homologs of all the S.
cerevisiae gene products required for the proper uptake of amino
acids (aa). In S. cerevisiae, amino acid permease family members,
including the SPS sensor component Ssy1p, depend upon the ER localized
packaging chaperone Shr3p to be correctly localized to the plasma
membrane. Consequently, shr3 mutants have greatly reduced
capacity to take up aa and are unable to respond to external aa cues.
These results indicate that Shr3p is the most upstream determinant of aa
uptake. CSH3 encodes the Candida Shr3p homolog that when
expressed in S. cerevisiae fully complements shr3 null
mutant phenotypes. We created null alleles of CSH3 to assess the
importance of aa in the growth and virulence of Candida. A C.
albicans csh3/csh3 null mutant has a reduced capacity to
take up aa, and is unable to switch morphologies in response to inducing
aa. CSH3/csh3 heterozygous strains display normal aa induced
morphological switching, but can not take up aa at wild-type rates.
Strikingly both CSH3/csh3 heterozygous and csh3/csh3
homozygous strains are unable to efficiently mount virulent infections
in a mouse model. The haploinsufficiency phenotypes indicate that both
CSH3 alleles contribute to maintain high capacity aa uptake in
wild-type strains. These results demonstrate that C. albicans
cells depend on aa, presumably due to their important role as nitrogen
sources, to grow efficiently in mammalian hosts.