Rapid Induction of High-frequency MTL Homozygosis and Microbiological Polymorphism in Candida albicans by Fluconazole

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Title:	Rapid Induction of High-frequency MTL Homozygosis and Microbiological Polymorphism in Candida albicans by Fluconazole
Authors:	Tsong-Yih Ou;Fang-Mo Chang;Ming-Li Chou;Wei-Ning Cheng;Kai-Cheng Lee;Che-
Keywords:	Candida albicans、fluconazole、mating type like gene、homozygosis
Date:	2011-08
Issue Date:	2012-01-19 09:11:07 (UTC+8)
Abstract:	Candida α lbicans is most common fungal pathogen of opportunistic infections. C. albicans was previously, noted as a diploid, apparently asexual fungus. Morphological and genetic studies had found mating type-like locus (MTL a/α) and demonstrated its relations to morphological switching, virulence, and f1uconazole-resistance. A parasexual cycle was found between opposite MTL homozygotes. However, C. albicans was found with MTL homozygous genotype in only around 3.2 % of clinical s仕ains ， and MTL heterozygotes had a low 企equency (about 10勻of white-opaque (刺刀0) switch to be MTL homozygotes in nature. In the present study, reference C. αlbicans strain SC5314 was used for f1uconazole-inducing assay to harvest 35 first-generation survival daughter strains from 70 colonies picked 企om f1uconazole inhibitory zone. Further separation with spreading culture and micromanipulator methods was further employed to gain second- and third-generation strains with accordance to first-generation daughter strains. PCR analysis based on MTL a1 ， α1 and cf2 was employed to demonstrate MTL genotypes of these isolates. Microscopic observation and f1owcytometry assay were employed for cell/colony morphology and DNA content analysis on progeny SC5314 and its daughter strains. High 企equency of MTL gene loss (24 of 35, 68.57 %) and homozygotes (16 of 鈣， 45.71 % ) were found in f1uconazole-inducing survival daughter strains with accordance to first-generation daughter strains. Polymorphism of ceIVcolony morphology and decreasing DNA content were also found in these f1uconazole-inducing daughter strains. Fluconazole treatment not only inhibited the growth of C. α lbicans but also altered phenotypic characteristics in ceIVcolony morphology as well as induced rapid highfrequency MTL gene loss and homozygosity in f1uconazole inhibition zone. The DNA content of these f1uconazole-inducing daughter strains were also obviously reduced with comparison to their progeny SC5314 suggesting a possibility of chromosome loss and DNA rearrangement during the f1uconazole treatment to C. albicαns.
Relation:	Asian Mycological Congress
Appears in Collections:	[Department of Internal Medicine] Periodical Articles

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