Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients
Jl. Lopez-ribot et al., Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients, ANTIM AG CH, 43(7), 1999, pp. 1621-1630
Mechanisms of resistance to azoles in Candida albicans, the main etiologic
agent of oropharyngeal candidiasis (OPC), include alterations in the target
enzyme (lanosterol demethylase) and increased efflux of drug. Previous stu
dies on mechanisms of resistance have been limited by the fact that only a
single isolate from each OPC episode was available for study. Multiple isol
ates from each OPC episode were evaluated with oral samples plated in CHROM
agar Candida with and without fluconazole to maximize detection of resistan
t yeasts. A total of 101 isolates from each of three serial episodes of OPC
from four different patients were evaluated. Decreasing geometric means of
fluconazole MICs with serial episodes of infection were detected in the fo
ur patients. However, 8-fold or larger (up to 32-fold) differences in fluco
nazole MICs were detected within isolates recovered at the same time point
in 7 of 12 episodes. Strain identity was analyzed by DNA typing techniques
and indicated that isolates from each patient represented mainly isogenic s
trains, but differed among patients. A Northern blot technique was used to
monitor expression of ERG11 (encoding lanosterol demethylase) and genes cod
ing for efflux pumps. This analysis revealed that clinical isolates obtaine
d from the same patient and episode were phenotypically heterogeneous in th
eir patterns of expression of these genes involved in fluconazole resistanc
e. These results demonstrate the complexity of the distribution of the mole
cular mechanisms of antifungal drug resistance and indicate that different
subpopulations of yeasts may coexist at a given time in the same patient an
d may develop resistance through different mechanisms.