• Title/Summary/Keyword: Azole resistance

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Azole Resistance Caused by Increased Drug Efflux in Candida glabrata Isolated from the Urinary Tract of a Dog with Diabetes Mellitus

  • Kim, Minchul;Lee, Hyekyung;Hwang, Sun-Young;Lee, Inhyung;Jung, Won Hee
    • Mycobiology
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    • v.45 no.4
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    • pp.426-429
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    • 2017
  • A yeast-like organism was isolated from a urine sample of a 6-year-old neutered male miniature poodle dog with urinary tract infection, diabetes ketoacidosis, and acute pancreatitis. We identified the yeast-like organism to be Candida glabrata and found that this fungus was highly resistant to azole antifungal drugs. To understand the mechanism of azole resistance in this isolate, the sequences and expression levels of the genes involved in drug resistance were analyzed. The results of our analysis showed that increased drug efflux, mediated by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of azole resistance of the C. glabrata isolated here.

Genomic Tandem Quadruplication is Associated with Ketoconazole Resistance in Malassezia pachydermatis

  • Kim, Minchul;Cho, Yong-Joon;Park, Minji;Choi, Yoojeong;Hwang, Sun Young;Jung, Won Hee
    • Journal of Microbiology and Biotechnology
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    • v.28 no.11
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    • pp.1937-1945
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    • 2018
  • Malassezia pachydermatis is a commensal yeast found on the skin of dogs. However, M. pachydermatis is also considered an opportunistic pathogen and is associated with various canine skin diseases including otitis externa and atopic dermatitis, which usually require treatment using an azole antifungal drug, such as ketoconazole. In this study, we isolated a ketoconazole-resistant strain of M. pachydermatis, designated "KCTC 27587," from the external ear canal of a dog with otitis externa and analyzed its resistance mechanism. To understand the mechanism underlying ketoconazole resistance of the clinical isolate M. pachydermatis KCTC 27587, the whole genome of the yeast was sequenced using the PacBio platform and was compared with M. pachydermatis type strain CBS 1879. We found that a ~84-kb region in chromosome 4 of M. pachydermatis KCTC 27587 was tandemly quadruplicated. The quadruplicated region contains 52 protein coding genes, including the homologs of ERG4 and ERG11, whose overexpression is known to be associated with azole resistance. Our data suggest that the quadruplication of the ~84-kb region may be the cause of the ketoconazole resistance in M. pachydermatis KCTC 27587.

Antifungal Susceptibility Tests and the cyp51 Mutant Strains among Clinical Aspergillus fumigatus Isolates from Korean Multicenters

  • Won, Eun Jeong;Joo, Min Young;Lee, Dain;Kim, Mi-Na;Park, Yeon-Joon;Kim, Soo Hyun;Shin, Myung Geun;Shin, Jong Hee
    • Mycobiology
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    • v.48 no.2
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    • pp.148-152
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    • 2020
  • We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

Decay of Populus cathay Treated with Paraffin Wax Emulsion and Copper Azole Compound

  • Liu, Jie;Liu, Min;Hou, Bingyi;Ma, Erni
    • Journal of the Korean Wood Science and Technology
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    • v.47 no.1
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    • pp.21-32
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    • 2019
  • In order to investigate the decay process of wood treated with preservative, waterproofing agent and their compound systems, a full-cell process was applied to impregnate the sapwood of poplar (Populus cathay) at paraffin wax emulsion concentrations of 0.5% and 2.0%, Copper Azole (CA) concentrations of 0.3% and 0.5%, and their four compound systems, respectively. Leaching tests and laboratory decay resistance against the white-rot fungus Corious versicolor (L.) Murrill for treated wood were carried out according to the America Standard E11-06 and China Standard GB/T 13942.1-2009. At certain time intervals during the decay test, samples were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction technique (XRD) to investigate the time-dependent changes of chemical components and crystalline structure, thus clarifying the decay mechanisms. The results suggested that white-rot fungi degrade hemicellulose and lignin in the wood cell wall first, followed by a simultaneous degradation of polysaccharides and lignin. Besides, CA could not only slower the decomposition of both hemicellulose and lignin, but also reduce the degradation amount of hemicellulose. However, paraffin wax emulsion at high concentration had a negative effect on the impregnation of CA for the compound system treated wood.

Widespread Occurrence of a CYP51A Pseudogene in Calonectria pseudonaviculata

  • Stravoravdis, Stefanos;LeBlanc, Nicholas R.;Marra, Robert E.;Crouch, Jo Anne;Hulvey, Jonathan P.
    • Mycobiology
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    • v.48 no.1
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    • pp.44-50
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    • 2020
  • Calonectria pseudonaviculata and C. henricotiae are two closely related fungal species responsible for boxwood blight disease of ornamental shrubs (Buxus spp.) in the U.S. and Europe. A previous study has shown isolates of the latter species, which is restricted to Europe, to be less sensitive to tetraconazole, an azole fungicide. In this study, we have analyzed the CYP51 paralogs for polymorphism in 26 genomes, representing geographically disparate populations of C. pseudonaviculata (n = 19) and C. henricotiae (n = 7), from the U.S., Europe, Asia, and New Zealand. The presence of a CYP51A pseudogene and lack of a functional CYP51A paralog in all C. pseudonaviculata genomes examined is a novel discovery for fungi and could have implications for the evolution of resistance to antifungal chemicals.

Identification and Functional Characterization of a Cryptococcus neoformans UPC2 Homolog

  • Kim, Nam-Kyun;Han, Kyung-Hwan;Jung, Won-Hee
    • Mycobiology
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    • v.38 no.3
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    • pp.215-218
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    • 2010
  • Azoles are currently the most widely used class of antifungal drugs clinically, and are effective for treating fungal infections. Target site of azoles is ergosterol biosynthesis in fungal cell membrane, which is absent in the mammalian host. However, the development of resistance to azole treatments in the fungal pathogen has become a significant challenge. Here, we report the identification and functional characterization of a UPC2 homolog in the human pathogen Cryptococcus neoformans. UPC2 plays roles in ergosterol biosynthesis, which is also affected by the availability of iron in Saccharomyces cerevisiae and Candida albicans. C. neoformans mutants lacking UPC2 were constructed, and a number of phenotypic characteristics, including antifungal susceptibility and iron utilization, were analyzed. No differences were found between the mutant phenotypes and wild type, suggesting that the role of C. neoformans UPC2 homolog may be different from those in S. cerevisiae and C. albicans, and that the gene may have a yet unknown function.

Efficacy of Wood Preservatives Formulated with Okara and Its Microscopic Analysis (두부비지 방부제의 방부효능 및 현미경적 분석)

  • Kim, Ho-Yong;Choi, In-Gyu;Ahn, Sye Hee;Oh, Sei Chang;Youn, Young Ho;Yang, In
    • Journal of the Korean Wood Science and Technology
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    • v.37 no.3
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    • pp.245-254
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    • 2009
  • As a substitute for CCA, which is inhibited due to its environmental pollution and human harmfulness, and CuAz and ACQ with a high cost, okara-based wood preservatives were formulated with okara hydrolyzates using copper sulfate and/or borax as a metal salt. The efficacy of the preservatives and X-ray microanalysis of wood specimens treated with the preservatives were examined to confirm the potential of the okara-based wood preservatives. Most of the preservatives showed excellent decay resistance against brown-rot fungi, Postia placenta and Gloeophyllum trabeum. The efficacy was improved when the acid concentration and temperature used for the hydrolysis of okara increased. In addition, when borax was added into copper sulfate/okara hydrolyzates preservative formulations, any decay was not found in the specimens. From the microscopic observation of the specimens treated with okara-based wood preservatives, it seems that okara is contributed to the fixing of metal salts in wood blocks. Therefore, it is speculated that okara-based wood preservatives can effectively protect wood against fungal attack as CuAz, and that the preservatives are sufficient to use as an alternative wood preservative of CCA, ACQ and CuAz.

Effect of Copper Retention on Copper Leaching in Wood Treated with Copper-based Preservatives

  • Ra, Jong-Bum;Kang, Sung-Mo;Kang, Shin-Kwon
    • Journal of the Korean Wood Science and Technology
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    • v.37 no.5
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    • pp.421-425
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    • 2009
  • This research investigates the effect of copper retention on copper leaching in wood treated with copper-based preservatives. Radiata pine (Pinus radiata D. Don) sapwood samples were ground in a Wiley mill equipped with a 20-mesh screen. The ground wood was vacuum-treated with various concentrations of alkaline copper quat (ACQ), bis-(N-cyclohexyl-diazeniumdioxy)-copper (CB-HDO), and copper azole (CUAZ). The treated samples were conditioned at $70^{\circ}C$ and 100% RH for 72 hours. The samples were leached by using the distilled water for four weeks, and the copper contents in each sample were measured by X-ray spectroscopy. As expected, the copper leaching was increased with increasing of copper retention. The copper leaching from the ACQ and CB-HDO treated samples were gradually decreased with increasing copper retention: however, the copper losses from the CUAZ treated samples appeared to be proportionally increased with the increase in copper retention in all retention levels tested. The results indicate that at the conditions of the same copper retention ACQ and CB-HDO treated wood have a better leaching resistance compared to CUAZ treated wood.