Volume 31, Number 5—May 2025
Research
Exponential Clonal Expansion of 5-Fluorocytosine–Resistant Candida tropicalis and New Insights into Underlying Molecular Mechanisms
Table 3
Overview of target gene mutations found in Candida tropicalis isolates in study of clonal expansion of 5-fluorocytosine–resistant C. tropicalis, Denmark
Amino acid alteration | Mutation type | No. strains | Total strains, N = 104 | Expected effect on protein | Modal MIC, mg/L (range)† |
---|---|---|---|---|---|
FCY2 | |||||
E49X | Nonsense (homozygous) | 30 (R) | 32 (R) | Premature termination, loss of function | >16, non–wild-type |
Q7X | Nonsense (homozygous) | 1 (R) | 32 (R) | Premature termination, loss of function | >16, non–wild-type |
K6NfsX10 | Single-nucleotide deletion (homozygous) | 1 (R) | 32 (R) | Frameshift leading to premature termination, loss of function | >16, non–wild-type |
E49X & M162I | Heterozygous | 12 (S) | 72 (S) | No significant impact on transporter function | 0.125 (0.06–0.5) |
H201I | Heterozygous | 1 (S) | 72 (S) | No significant impact on transporter function | 0.125 |
I473L | Heterozygous | 2 (S) | 72 (S) | No significant impact on transporter function | (0.06–0.125) |
M130T | Heterozygous | 1 (S) | 72 (S) | No significant impact on transporter function | 0.25 |
M162I | Heterozygous | 1 (S) | 72 (S) | No significant impact on transporter function | 0.125 |
S108F | Heterozygous | 1 (S) | 72 (S) | No significant impact on transporter function | 0.06 |
W67X | Heterozygous | 1 (S) | 72 (S) | Discrete impact on transporter function | 0.5 |
S258X |
Heterozygous |
1 (S) |
72 (S) |
No significant impact on transporter function |
0.25 |
FUR1 | |||||
K5Q & A157S |
Homozygous |
1 (S) |
72 (S) |
No impact on 5-FC conversion |
0.125 (0.06–0.5) |
URA3 | |||||
K177E | Homozygous | 30 (R) + 2 (S) | 32 (R) + 72 (S) | No impact on protein function | 0.125 (0.06–0.5) |
*Strains were wild-type except as indicated. FCY2, purine-cytosine permease; FUR1, uracil phosphoribosyltransferase; R, resistant (non–wild-type); S, susceptible (wild-type); URA3, orotidine-5'-phosphate decarboxylase †Modal MIC value presented for alterations represented by >10 isolates, MIC range in parentheses for alterations represented by <10 isolates, and MIC value for alterations found in a single isolate. For comparison, modal MIC for wild-type population is 0.125 mg/L.