Adaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicans
  • Metaadatok
Tartalom: https://publikacio.ppke.hu/id/eprint/1684/
Archívum: PPKE Publikáció Repozitórium
Gyűjtemény: Állapot = Megjelent
Szakterület = 01. Természettudományok: 01.06. Biológiai tudományok: 01.06.03. Biokémia és molekuláris biológia
Típus = Folyóiratcikk
Cím:
Adaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicans
Létrehozó:
Weil Tobias
Santamaria Rodrigo
Lee Wanseon
Rung Johan
Tocci Noemi
Abbey Darren
Bezerra Ana R.
Carreto Laura
Moura Gabriela R.
Bayes Monica
Gut Ivo G.
Csikász-Nagy Attila
Cavalieri Duccio
Berman Judith
Santos Manuel A. S.
Dátum:
2017
Téma:
01.06.03. Biokémia és molekuláris biológia
Tartalmi leírás:
Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole. Genome sequencing, array-based comparative genome analysis, and gene expression profiling revealed that during the course of evolution in fluconazole, the range of mutational and gene deregulation differences was distinctively different and broader in the hypermistranslating strain, including multiple chromosome duplications, partial chromosome deletions, and polyploidy. Especially, the increased accumulation of loss-ofheterozygosity events, aneuploidy, translational and cell surface modifications, and differences in drug efflux seem to mediate more rapid drug resistance acquisition under mistranslation. Our observations support a pivotal role for adaptive mistranslation in the evolution of drug resistance in C. albicans.
Nyelv:
angol
angol
Típus:
Folyóiratcikk
PeerReviewed
Formátum:
text
Azonosító:
Weil Tobias; Santamaria Rodrigo; Lee Wanseon; Rung Johan; Tocci Noemi; Abbey Darren; Bezerra Ana R.; Carreto Laura; Moura Gabriela R.; Bayes Monica; Gut Ivo G.; Csikász-Nagy Attila; Cavalieri Duccio; Berman Judith; Santos Manuel A. S.: Adaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicans. mSPHERE, 2 (4). ISSN 2379-5042 (2017)
MTMT:30439623 10.1128/mSphere.00167-17
Kapcsolat:
MTMT:30439623 10.1128/mSphere.00167-17