Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans

Tsong Yih Ou, Fang Mo Chang, Wei Ning Cheng, Adela Lara, Ming Li Chou, Wei Fang Lee, Kai Cheng Lee, Che Tong Lin, Wen Sen Lee, Fang Lan Yu, Ching Hua Su

Research output: Contribution to journalArticle

Abstract

Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α). Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2% of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10-4) of white-opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314) was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6%) in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans.

Original languageEnglish
JournalJournal of Microbiology, Immunology and Infection
DOIs
Publication statusPublished - 2017

Fingerprint

Fluconazole
Candida albicans
Homozygote
Invasive Candidiasis
Loss of Heterozygosity
DNA
Opportunistic Infections
Heterozygote
Diploidy
Fungi
Genotype
Polymerase Chain Reaction
Growth
Pharmaceutical Preparations

Keywords

  • Candida albicans
  • Fluconazole
  • Loss of heterozygosity
  • Mating type-like gene

ASJC Scopus subject areas

  • Microbiology (medical)
  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Infectious Diseases

Cite this

Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans. / Ou, Tsong Yih; Chang, Fang Mo; Cheng, Wei Ning; Lara, Adela; Chou, Ming Li; Lee, Wei Fang; Lee, Kai Cheng; Lin, Che Tong; Lee, Wen Sen; Yu, Fang Lan; Su, Ching Hua.

In: Journal of Microbiology, Immunology and Infection, 2017.

Research output: Contribution to journalArticle

Ou, Tsong Yih ; Chang, Fang Mo ; Cheng, Wei Ning ; Lara, Adela ; Chou, Ming Li ; Lee, Wei Fang ; Lee, Kai Cheng ; Lin, Che Tong ; Lee, Wen Sen ; Yu, Fang Lan ; Su, Ching Hua. / Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans. In: Journal of Microbiology, Immunology and Infection. 2017.
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abstract = "Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α). Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2{\%} of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10-4) of white-opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314) was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6{\%}) in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans.",
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author = "Ou, {Tsong Yih} and Chang, {Fang Mo} and Cheng, {Wei Ning} and Adela Lara and Chou, {Ming Li} and Lee, {Wei Fang} and Lee, {Kai Cheng} and Lin, {Che Tong} and Lee, {Wen Sen} and Yu, {Fang Lan} and Su, {Ching Hua}",
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T1 - Fluconazole induces rapid high-frequency MTL homozygosis with microbiological polymorphism in Candida albicans

AU - Ou, Tsong Yih

AU - Chang, Fang Mo

AU - Cheng, Wei Ning

AU - Lara, Adela

AU - Chou, Ming Li

AU - Lee, Wei Fang

AU - Lee, Kai Cheng

AU - Lin, Che Tong

AU - Lee, Wen Sen

AU - Yu, Fang Lan

AU - Su, Ching Hua

PY - 2017

Y1 - 2017

N2 - Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α). Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2% of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10-4) of white-opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314) was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6%) in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans.

AB - Background: Candida albicans, a common fungal pathogen that can cause opportunistic infections, is regarded as an apparently asexual, diploid fungus. A parasexual cycle was previously found between homozygotes with opposite mating type-like loci (MTLa/α). Fluconazole-resistant strains had a higher proportion of MTL homozygotes, whereas MTL homozygous C. albicans was found in only about 3.2% of clinical strains. MTL heterozygotes had a low frequency (1.4 × 10-4) of white-opaque switching to MTL homozygotes in nature. Methods: Here, a reference C. albicans strain (SC5314) was used in a fluconazole-induced assay to obtain standard opaque MTL homozygous strains and first-generation daughter strains from the fluconazole inhibition zone. Further separation methods were employed to produce second- and third-generation daughter strains. Polymerase chain reaction analysis based on MTL genes was used to define MTL genotypes, and microscopic observations, a flow-cytometric assay, and an antifungal E-test were used to compare microbiological characteristics. Results: MTL homozygotes were found at a high frequency (17 of 35; 48.6%) in fluconazole-induced first-generation daughter strains, as were morphological polymorphisms, decreased DNA content, and modified antifungal drug susceptibility. High-frequency MTL homozygosity was identified inside the fluconazole inhibition zone within 24 hours. The DNA content of fluconazole-induced daughter strains was reduced compared with their progenitor SC5314 and standard MTL homozygous strains. Conclusion: Treatment with fluconazole, commonly used to treat invasive candidiasis, inhibited the growth of C. albicans and altered its microbiological characteristics. Our results suggest that fluconazole treatment induces the high frequency of loss of heterozygosity and microbiological polymorphism in C. albicans.

KW - Candida albicans

KW - Fluconazole

KW - Loss of heterozygosity

KW - Mating type-like gene

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