In Candida albicans, resistance to flucytosine and terbinafine is linked to MAT locus homozygosity and multilocus sequence typing clade 1.
A panel of 637 isolates of Candida albicans that had been typed by multilocus sequence typing (MLST) and tested for susceptibility to amphotericin B, caspofungin, fluconazole, flucytosine, itraconazole, ketoconazole, miconazole, terbinafine and voriconazole was the material for a statistical analysis of possible associations between antifungal susceptibility and other properties. For terbinafine and flucytosine, the greatest proportion of low-susceptibility isolates, judged by two resistance breakpoints, was found in MLST clade 1 and among isolates homozygous at the MAT locus, although only three isolates showed cross-resistance to the two agents. Most instances of low susceptibility to azoles, flucytosine and terbinafine were among oropharyngeal isolates from HIV-positive individuals. Statistically significant correlations were found between terbinafine and azole minimal inhibitory concentrations (MICs), while correlations between flucytosine MICs and azole MICs were less strong. It is concluded that a common regulatory mechanism may operate to generate resistance to the two classes of agent that inhibit ergosterol biosynthesis, terbinafine and the azoles, but that flucytosine resistance, although still commonly associated with MAT homozygosity, is differently regulated.
Aberdeen Fungal Group, School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK. f.odds@abdn.ac.uk
Frank C
FC
Odds
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D016172:DNA Fingerprinting; D025141:Drug Resistance, Fungal; D005437:Flucytosine / Q000494:pharmacology*; D005838:Genotype; D015658:HIV Infections / Q000150:complications; D006720:Homozygote; D006801:Humans; D000072235:Mating Factor; D008826:Microbial Sensitivity Tests; D016533:Mycological Typing Techniques; D009281:Naphthalenes / Q000494:pharmacology*; D009960:Oropharynx / Q000382:microbiology; D010455:Peptides / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000077291:Terbinafine
D000935:Antifungal Agents; D009281:Naphthalenes; D010455:Peptides; D000072235:Mating Factor; D005437:Flucytosine; D000077291:Terbinafine