Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility
Cryptococcosis, one of the most important systemic mycosis in the world, is caused by different genotypes of Cryptococcus neoformans and Cryptococcus gattii, which differ in their ecology, epidemiology, and antifungal susceptibility. Therefore, the search for new molecular markers for genotyping, pa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00086/full |
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| author | Felipe E. E. S. Gomes Felipe E. E. S. Gomes Thales D. Arantes Thales D. Arantes José A. L. Fernandes Leonardo C. Ferreira Leonardo C. Ferreira Héctor Romero Sandra M. G. Bosco Maria T. B. Oliveira Gilda M. B. Del Negro Raquel C. Theodoro |
| author_facet | Felipe E. E. S. Gomes Felipe E. E. S. Gomes Thales D. Arantes Thales D. Arantes José A. L. Fernandes Leonardo C. Ferreira Leonardo C. Ferreira Héctor Romero Sandra M. G. Bosco Maria T. B. Oliveira Gilda M. B. Del Negro Raquel C. Theodoro |
| author_sort | Felipe E. E. S. Gomes |
| collection | DOAJ |
| description | Cryptococcosis, one of the most important systemic mycosis in the world, is caused by different genotypes of Cryptococcus neoformans and Cryptococcus gattii, which differ in their ecology, epidemiology, and antifungal susceptibility. Therefore, the search for new molecular markers for genotyping, pathogenicity and drug susceptibility is necessary. Group I introns fulfill the requisites for such task because (i) they are polymorphic sequences; (ii) their self-splicing is inhibited by some drugs; and (iii) their correct splicing under parasitic conditions is indispensable for pathogen survival. Here, we investigated the presence of group I introns in the mitochondrial LSU rRNA gene in 77 Cryptococcus isolates and its possible relation to drug susceptibility. Sequencing revealed two new introns in the LSU rRNA gene. All the introns showed high sequence similarity to other mitochondrial introns from distinct fungi, supporting the hypothesis of an ancient non-allelic invasion. Intron presence was statistically associated with those genotypes reported to be less pathogenic (p < 0.001). Further virulence assays are needed to confirm this finding. In addition, in vitro antifungal tests indicated that the presence of LSU rRNA introns may influence the minimum inhibitory concentration (MIC) of amphotericin B and 5-fluorocytosine. These findings point to group I introns in the mitochondrial genome of Cryptococcus as potential molecular markers for antifungal resistance, as well as therapeutic targets. |
| first_indexed | 2024-12-14T20:02:53Z |
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| id | doaj.art-7ab1d4070746482da26c0a916aabd4c6 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T20:02:53Z |
| publishDate | 2018-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7ab1d4070746482da26c0a916aabd4c62022-12-21T22:49:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-02-01910.3389/fmicb.2018.00086323395Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug SusceptibilityFelipe E. E. S. Gomes0Felipe E. E. S. Gomes1Thales D. Arantes2Thales D. Arantes3José A. L. Fernandes4Leonardo C. Ferreira5Leonardo C. Ferreira6Héctor Romero7Sandra M. G. Bosco8Maria T. B. Oliveira9Gilda M. B. Del Negro10Raquel C. Theodoro11Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, BrazilInstitute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, BrazilDepartment of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, BrazilInstitute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, BrazilInstitute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, BrazilDepartment of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, BrazilInstitute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, BrazilLaboratorio de Organizacion y Evolución del Genoma/Unidad de Genómica Evolutiva, Departamento de Ecología y Evolución, Facultad de Ciencias/CURE, Universidad de la República, Maldonado, UruguayDepartment of Microbiology and Immunology, Institute of Biosciences, Universidade Estadual Paulista Julio de Mesquita Filho, São Paulo, BrazilDepartment of Microbiology and Parasitology, Universidade Federal do Rio Grande do Norte, Natal, BrazilInstitute of Tropical Medicine of São Paulo, Universidade de São Paulo, São Paulo, BrazilInstitute of Tropical Medicine of Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, BrazilCryptococcosis, one of the most important systemic mycosis in the world, is caused by different genotypes of Cryptococcus neoformans and Cryptococcus gattii, which differ in their ecology, epidemiology, and antifungal susceptibility. Therefore, the search for new molecular markers for genotyping, pathogenicity and drug susceptibility is necessary. Group I introns fulfill the requisites for such task because (i) they are polymorphic sequences; (ii) their self-splicing is inhibited by some drugs; and (iii) their correct splicing under parasitic conditions is indispensable for pathogen survival. Here, we investigated the presence of group I introns in the mitochondrial LSU rRNA gene in 77 Cryptococcus isolates and its possible relation to drug susceptibility. Sequencing revealed two new introns in the LSU rRNA gene. All the introns showed high sequence similarity to other mitochondrial introns from distinct fungi, supporting the hypothesis of an ancient non-allelic invasion. Intron presence was statistically associated with those genotypes reported to be less pathogenic (p < 0.001). Further virulence assays are needed to confirm this finding. In addition, in vitro antifungal tests indicated that the presence of LSU rRNA introns may influence the minimum inhibitory concentration (MIC) of amphotericin B and 5-fluorocytosine. These findings point to group I introns in the mitochondrial genome of Cryptococcus as potential molecular markers for antifungal resistance, as well as therapeutic targets.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00086/fullgroup I intronsmtDNALSUCryptococcus genotypesantifungal susceptibility5-fluorocytosine |
| spellingShingle | Felipe E. E. S. Gomes Felipe E. E. S. Gomes Thales D. Arantes Thales D. Arantes José A. L. Fernandes Leonardo C. Ferreira Leonardo C. Ferreira Héctor Romero Sandra M. G. Bosco Maria T. B. Oliveira Gilda M. B. Del Negro Raquel C. Theodoro Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility Frontiers in Microbiology group I introns mtDNA LSU Cryptococcus genotypes antifungal susceptibility 5-fluorocytosine |
| title | Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility |
| title_full | Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility |
| title_fullStr | Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility |
| title_full_unstemmed | Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility |
| title_short | Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility |
| title_sort | polymorphism in mitochondrial group i introns among cryptococcus neoformans and cryptococcus gattii genotypes and its association with drug susceptibility |
| topic | group I introns mtDNA LSU Cryptococcus genotypes antifungal susceptibility 5-fluorocytosine |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00086/full |
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