Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization
The pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients ad...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.01585/full |
| _version_ | 1819129344878968832 |
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| author | Olga Rivero-Menendez Patricia Navarro-Rodriguez Leticia Bernal-Martinez Leticia Bernal-Martinez Gema Martin-Cano Laura Lopez-Perez Isabel Sanchez-Romero Ana Perez-Ayala Javier Capilla Oscar Zaragoza Oscar Zaragoza Ana Alastruey-Izquierdo Ana Alastruey-Izquierdo |
| author_facet | Olga Rivero-Menendez Patricia Navarro-Rodriguez Leticia Bernal-Martinez Leticia Bernal-Martinez Gema Martin-Cano Laura Lopez-Perez Isabel Sanchez-Romero Ana Perez-Ayala Javier Capilla Oscar Zaragoza Oscar Zaragoza Ana Alastruey-Izquierdo Ana Alastruey-Izquierdo |
| author_sort | Olga Rivero-Menendez |
| collection | DOAJ |
| description | The pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins. |
| first_indexed | 2024-12-22T08:42:14Z |
| format | Article |
| id | doaj.art-5835a54a45ef404691d1311bb02fc5b5 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T08:42:14Z |
| publishDate | 2019-07-01 |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-5835a54a45ef404691d1311bb02fc5b52022-12-21T18:32:12ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-07-011010.3389/fmicb.2019.01585466748Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular CharacterizationOlga Rivero-Menendez0Patricia Navarro-Rodriguez1Leticia Bernal-Martinez2Leticia Bernal-Martinez3Gema Martin-Cano4Laura Lopez-Perez5Isabel Sanchez-Romero6Ana Perez-Ayala7Javier Capilla8Oscar Zaragoza9Oscar Zaragoza10Ana Alastruey-Izquierdo11Ana Alastruey-Izquierdo12Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, SpainUnitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Tarragona, SpainMycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, SpainSpanish Network for the Research in Infectious Diseases (RD16CIII/0004/0003), Instituto de Salud Carlos III, Madrid, SpainMycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, SpainMycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, SpainHospital Universitario Puerta de Hierro, Madrid, SpainHospital Universitario 12 de Octubre, Madrid, SpainUnitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Tarragona, SpainMycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, SpainSpanish Network for the Research in Infectious Diseases (RD16CIII/0004/0003), Instituto de Salud Carlos III, Madrid, SpainMycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, SpainSpanish Network for the Research in Infectious Diseases (RD16CIII/0004/0003), Instituto de Salud Carlos III, Madrid, SpainThe pathogenic yeast Candida glabrata has become a public health issue due to the increasing number of echinocandin resistant clinical strains reported. In this study, acquisition and development of resistance to this antifungal class were studied in serial C. glabrata isolates from five patients admitted in two Spanish hospitals with a resistant profile against echinocandins associated with different mutations in hot-spot 1 of FKS2 gene. For two of these patients susceptible FKS wild-type isolates obtained prior to resistant ones were also investigated. Isolates were genotyped using multilocus sequence typing and microsatellite length polymorphism techniques, which yielded comparable results. Susceptible and resistant isolates from the same patient had the same genotype, being sequence type (ST) 3 the most prevalent among them. Isolates with different FKS mutations but the same ST were present in the same patient. MSH2 gene alterations were also studied to investigate their correlation with antifungal resistance acquisition but no association was found with antifungal resistance nor with specific genotypes. In vitro exposure to increasing concentrations of micafungin to susceptible isolates developed colonies carrying FKS mutations in agar plates containing a minimum concentration of 0.06 mg/L of micafungin after less than 48 h of exposure. We investigated the correlation between development of resistance and genotype in a set of susceptible strains after being in vitro exposed to micafungin and anidulafungin but no correlation was found. Mutant prevention concentration values and spontaneous growth frequencies after selection with both echinocandins were statistically similar, although FKS mutant colonies were more abundant after micafungin exposure (p < 0.001). Mutation S663P and F659 deletion were the most common ones found after selection with both echinocandins.https://www.frontiersin.org/article/10.3389/fmicb.2019.01585/fullCandida glabrataechinocandinsantifungal resistanceFKSMSH2genotyping |
| spellingShingle | Olga Rivero-Menendez Patricia Navarro-Rodriguez Leticia Bernal-Martinez Leticia Bernal-Martinez Gema Martin-Cano Laura Lopez-Perez Isabel Sanchez-Romero Ana Perez-Ayala Javier Capilla Oscar Zaragoza Oscar Zaragoza Ana Alastruey-Izquierdo Ana Alastruey-Izquierdo Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization Frontiers in Microbiology Candida glabrata echinocandins antifungal resistance FKS MSH2 genotyping |
| title | Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization |
| title_full | Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization |
| title_fullStr | Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization |
| title_full_unstemmed | Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization |
| title_short | Clinical and Laboratory Development of Echinocandin Resistance in Candida glabrata: Molecular Characterization |
| title_sort | clinical and laboratory development of echinocandin resistance in candida glabrata molecular characterization |
| topic | Candida glabrata echinocandins antifungal resistance FKS MSH2 genotyping |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.01585/full |
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