Adaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicans

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)

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Folyóiratcikk

Szerző azonosítók:

Név	ORCID	MTMT szerző 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	0000-0002-2919-5601	10012379
Cavalieri Duccio
Berman Judith	0000-0002-8577-0084
Santos Manuel A. S.

Absztrakt (kivonat):

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.

Folyóirat/kiadvány címe:

mSPHERE

Évszám:

2017

Kötet:

Szám:

ISSN:

2379-5042

Intézmény:

Pázmány Péter Katolikus Egyetem

Kar:

Információs Technológiai és Bionikai Kar (2013.07.-)