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ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait
Suhail Ahmad,
Leena Joseph,
Josie Parker,
Mohammad Asadzadeh,
Steven Kelly
,
Jacques F. Meis,
Ziauddin Khan
Antimicrobial Agents and Chemotherapy, Volume: 63, Issue: 2, Start page: e01900-18
Swansea University Authors:
Josie Parker, Steven Kelly
-
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DOI (Published version): 10.1128/AAC.01900-18
Abstract
Candida glabrata is intrinsically less susceptible to azoles and resistance to echinocandins and reduced susceptibility to amphotericin B has also been detected. Molecular mechanisms of reduced susceptibility (RS) to amphotericin B (AMB) were investigated in C. glabrata strains in Kuwait by sequence...
Published in: | Antimicrobial Agents and Chemotherapy |
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ISSN: | 0066-4804 1098-6596 |
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2018
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URI: | https://cronfa.swan.ac.uk/Record/cronfa45903 |
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2020-07-17T13:16:36.0403611 v2 45903 2018-11-12 ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait e563ed4e1c7db8d1e131fb78a5f8d0d5 Josie Parker Josie Parker true false b17cebaf09b4d737b9378a3581e3de93 0000-0001-7991-5040 Steven Kelly Steven Kelly true false 2018-11-12 FGMHL Candida glabrata is intrinsically less susceptible to azoles and resistance to echinocandins and reduced susceptibility to amphotericin B has also been detected. Molecular mechanisms of reduced susceptibility (RS) to amphotericin B (AMB) were investigated in C. glabrata strains in Kuwait by sequence analyses of genes involved in ergosterol biosynthesis. A total of 1646 C. glabrata isolates were tested by Etest and results for 12 selected isolates were confirmed by reference broth microdilution. PCR-sequencing of three (ERG2, ERG6 and ERG11) genes was performed for all RS-AMB and 5 selected wild-type C. glabrata isolates by using gene-specific primers. Total cell sterol content was analyzed by gas chromatography-mass spectrometry. Phylogenetic relationship among the isolates was investigated by multilocus sequence typing. Wild-type isolates contained only synonymous mutations in ERG2, ERG6 or ERG11 and total sterol content was similar to reference strains. A nonsynonymous (AGA48AAA, R48K) ERG6 mutation was found in both RS-AMB and wild-type isolates. Four RS-AMB isolates contained novel nonsense mutations at Trp286/Tyr192/Leu341 and 2 isolates contained nonsynonymous (V126F or C198F) mutation in ERG6 and their sterol content were consistent with ERG6 deficiency. Two other RS-AMB isolates contained a novel nonsynonymous (G119S or G122S) ERG2 mutation and their sterol content were consistent with ERG2 deficiency. Of 8 RS-AMB isolates, 1 fluconazole-resistant isolate also contained nonsynonymous Y141H+L381M mutations while 7 isolates contained only synonymous mutations in ERG11. All isolates with ERG6/ERG2/ERG11 mutations were genotypically distinct strains. Our data show that ERG6 and ERG2 are major targets conferring RS-AMB in clinical C. glabrata isolates. Journal Article Antimicrobial Agents and Chemotherapy 63 2 e01900-18 0066-4804 1098-6596 19 11 2018 2018-11-19 10.1128/AAC.01900-18 COLLEGE NANME Medicine, Health and Life Science - Faculty COLLEGE CODE FGMHL Swansea University 2020-07-17T13:16:36.0403611 2018-11-12T14:16:55.2891878 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Suhail Ahmad 1 Leena Joseph 2 Josie Parker 3 Mohammad Asadzadeh 4 Steven Kelly 0000-0001-7991-5040 5 Jacques F. Meis 6 Ziauddin Khan 7 0045903-12112018141921.pdf 45903.pdf 2018-11-12T14:19:21.6070000 Output 255085 application/pdf Accepted Manuscript true 2019-05-19T00:00:00.0000000 true eng |
title |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait |
spellingShingle |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait Josie Parker Steven Kelly |
title_short |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait |
title_full |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait |
title_fullStr |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait |
title_full_unstemmed |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait |
title_sort |
ERG6 and ERG2 Are Major Targets Conferring Reduced Susceptibility to Amphotericin B in Clinical Candida glabrata Isolates in Kuwait |
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e563ed4e1c7db8d1e131fb78a5f8d0d5 b17cebaf09b4d737b9378a3581e3de93 |
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e563ed4e1c7db8d1e131fb78a5f8d0d5_***_Josie Parker b17cebaf09b4d737b9378a3581e3de93_***_Steven Kelly |
author |
Josie Parker Steven Kelly |
author2 |
Suhail Ahmad Leena Joseph Josie Parker Mohammad Asadzadeh Steven Kelly Jacques F. Meis Ziauddin Khan |
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Antimicrobial Agents and Chemotherapy |
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63 |
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e01900-18 |
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2018 |
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10.1128/AAC.01900-18 |
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Faculty of Medicine, Health and Life Sciences |
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description |
Candida glabrata is intrinsically less susceptible to azoles and resistance to echinocandins and reduced susceptibility to amphotericin B has also been detected. Molecular mechanisms of reduced susceptibility (RS) to amphotericin B (AMB) were investigated in C. glabrata strains in Kuwait by sequence analyses of genes involved in ergosterol biosynthesis. A total of 1646 C. glabrata isolates were tested by Etest and results for 12 selected isolates were confirmed by reference broth microdilution. PCR-sequencing of three (ERG2, ERG6 and ERG11) genes was performed for all RS-AMB and 5 selected wild-type C. glabrata isolates by using gene-specific primers. Total cell sterol content was analyzed by gas chromatography-mass spectrometry. Phylogenetic relationship among the isolates was investigated by multilocus sequence typing. Wild-type isolates contained only synonymous mutations in ERG2, ERG6 or ERG11 and total sterol content was similar to reference strains. A nonsynonymous (AGA48AAA, R48K) ERG6 mutation was found in both RS-AMB and wild-type isolates. Four RS-AMB isolates contained novel nonsense mutations at Trp286/Tyr192/Leu341 and 2 isolates contained nonsynonymous (V126F or C198F) mutation in ERG6 and their sterol content were consistent with ERG6 deficiency. Two other RS-AMB isolates contained a novel nonsynonymous (G119S or G122S) ERG2 mutation and their sterol content were consistent with ERG2 deficiency. Of 8 RS-AMB isolates, 1 fluconazole-resistant isolate also contained nonsynonymous Y141H+L381M mutations while 7 isolates contained only synonymous mutations in ERG11. All isolates with ERG6/ERG2/ERG11 mutations were genotypically distinct strains. Our data show that ERG6 and ERG2 are major targets conferring RS-AMB in clinical C. glabrata isolates. |
published_date |
2018-11-19T03:57:34Z |
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1763752913732108288 |
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11.017776 |