ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients
Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collect...
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| Published in | Asian Pacific journal of tropical biomedicine Vol. 5; no. 11; pp. 909 - 914 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Elsevier B.V
01.11.2015
Wolters Kluwer Medknow Publications |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collected.Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans(2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced.Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total,27 missense mutations were detected in ERG11 genes from resistant/susceptible dosedependent isolates. Among them, Y132 H, A114 S, and Y257 H substitutions were most prevalent and were known to cause fluconazole resistance. G464 S and F72 S also have been proved to cause fluconazole resistance. Two novel substitutions(T285A, S457P) in hotspot regions were identified.Conclusions: Twenty seven mutations in the ERG11 gene were identified in azoleresistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions(T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis. |
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| AbstractList | Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collected.Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans(2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced.Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total,27 missense mutations were detected in ERG11 genes from resistant/susceptible dosedependent isolates. Among them, Y132 H, A114 S, and Y257 H substitutions were most prevalent and were known to cause fluconazole resistance. G464 S and F72 S also have been proved to cause fluconazole resistance. Two novel substitutions(T285A, S457P) in hotspot regions were identified.Conclusions: Twenty seven mutations in the ERG11 gene were identified in azoleresistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions(T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis. Objective: To investigate the azole susceptibility of Candida albicans (C. albicans) from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance. Methods: Three hundred and two clinical isolates of Candida species were collected. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans (2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced. Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and 4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total, 27 missense mutations were detected in ERG11 genes from resistant/susceptible dose-dependent isolates. Among them, Y132H, A114S, and Y257H substitutions were most prevalent and were known to cause fluconazole resistance. G464S and F72S also have been proved to cause fluconazole resistance. Two novel substitutions (T285A, S457P) in hotspot regions were identified. Conclusions: Twenty seven mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions (T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis. To investigate the azole susceptibility of Candida albicans (C. albicans) from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance. Three hundred and two clinical isolates of Candida species were collected. Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans (2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced. Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and 4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total, 27 missense mutations were detected in ERG11 genes from resistant/susceptible dose-dependent isolates. Among them, Y132H, A114S, and Y257H substitutions were most prevalent and were known to cause fluconazole resistance. G464S and F72S also have been proved to cause fluconazole resistance. Two novel substitutions (T285A, S457P) in hotspot regions were identified. Twenty seven mutations in the ERG11 gene were identified in azole-resistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions (T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis. |
| Author | Bin Wang Li-Hua Huang Ji-Xue Zhao Man Wei Hua Fang Dan-Yang Wang Hong-Fa Wang Ji-Gang Yin Mei Xiang |
| AuthorAffiliation | The Second Hospital of Jilin University,Key Lab of Zoonosis,Ministry of Education The First Hospital of Jilin University Shandong Institute of Parasitic Diseases Key Lab of Zoonosis,Ministry of Education,Institute of Zoonosis,Jilin University |
| Author_xml | – sequence: 1 givenname: Bin surname: Wang fullname: Wang, Bin organization: The Second Hospital of Jilin University, Key Lab of Zoonosis, Ministry of Education, Changchun 130041, China – sequence: 2 givenname: Li-Hua surname: Huang fullname: Huang, Li-Hua organization: The Second Hospital of Jilin University, Key Lab of Zoonosis, Ministry of Education, Changchun 130041, China – sequence: 3 givenname: Ji-Xue surname: Zhao fullname: Zhao, Ji-Xue organization: The First Hospital of Jilin University, Changchun 130041, China – sequence: 4 givenname: Man surname: Wei fullname: Wei, Man organization: The Second Hospital of Jilin University, Key Lab of Zoonosis, Ministry of Education, Changchun 130041, China – sequence: 5 givenname: Hua surname: Fang fullname: Fang, Hua organization: The Second Hospital of Jilin University, Key Lab of Zoonosis, Ministry of Education, Changchun 130041, China – sequence: 6 givenname: Dan-Yang surname: Wang fullname: Wang, Dan-Yang organization: The Second Hospital of Jilin University, Key Lab of Zoonosis, Ministry of Education, Changchun 130041, China – sequence: 7 givenname: Hong-Fa surname: Wang fullname: Wang, Hong-Fa organization: Shandong Institute of Parasitic Diseases, Jining 272033, China – sequence: 8 givenname: Ji-Gang surname: Yin fullname: Yin, Ji-Gang email: yinjg0924@sina.com organization: Key Lab of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China – sequence: 9 givenname: Mei surname: Xiang fullname: Xiang, Mei email: xiangmei1971@sina.com organization: The Second Hospital of Jilin University, Key Lab of Zoonosis, Ministry of Education, Changchun 130041, China |
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| Keywords | Candida albicans Azoles resistance Vulvovaginal candidosis Mutation ERG11 gene |
| Language | English |
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| Notes | Candida albicans Azoles resistance ERG11 gene Muta Objective: To investigate the azole susceptibility of Candida albicans(C.albicans)from vulvovaginal candidosis patients and to analyze the relationship between ERG11 gene mutations in these isolates and azole resistance.Methods: Three hundred and two clinical isolates of Candida species were collected.Azole susceptibility was tested in vitro in microdilution studies. The ERG11 genes of 17 isolates of C. albicans(2 susceptibles, 5 dose-dependent resistants and 10 resistants) were amplified and sequenced.Results: Of the 302 isolates collected, 70.2% were C. albicans, of which 8.5%, 3.8% and4.2% were resistant to fluconazole, itraconazole and voriconazole, respectively. In total,27 missense mutations were detected in ERG11 genes from resistant/susceptible dosedependent isolates. Among them, Y132 H, A114 S, and Y257 H substitutions were most prevalent and were known to cause fluconazole resistance. G464 S and F72 S also have been proved to cause fluconazole resistance. Two novel substitutions(T285A, S457P) in hotspot regions were identified.Conclusions: Twenty seven mutations in the ERG11 gene were identified in azoleresistant C. albicans isolates, which indicated a possible relation with the increase in resistance to azole drugs and the recurrence of vulvovaginal candidosis. The relationship of two novel substitutions(T285A, S457P) with fluconazole resistance needs to be further verified by site-directed mutagenesis. Bin Wang;Li-Hua Huang;Ji-Xue Zhao;Man Wei;Hua Fang;Dan-Yang Wang;Hong-Fa Wang;Ji-Gang Yin;Mei Xiang;The Second Hospital of Jilin University,Key Lab of Zoonosis,Ministry of Education;The First Hospital of Jilin University;Shandong Institute of Parasitic Diseases;Key Lab of Zoonosis,Ministry of Education,Institute of Zoonosis,Jilin University |
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| PublicationDate | November 2015 |
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| PublicationTitle | Asian Pacific journal of tropical biomedicine |
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| Publisher | Elsevier B.V Wolters Kluwer Medknow Publications |
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| Title | ERG11 mutations associated with azole resistance in Candida albicans isolates from vulvovaginal candidosis patients |
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