Artículo
Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance
Ben Ami, Ronen; Garcia, Guillermo Manuel
; Lewis, Rusell E.; Gamarra, Maria Soledad; Leventakos, Konstantinos; Perlin, David S.; Kontoyiannis, Dimitrios P.
Fecha de publicación:
08/2011
Editorial:
University of Chicago Press
Revista:
Journal Of Infectious Diseases
ISSN:
0022-1899
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The identification of FKS1 mutations in Candida albicans associated with echinocandin resistance has raised concerns over the spread of drug-resistant strains. We studied the impact of fks1 mutations on C. albicans virulence and fitness. Compared with wild-type strains for FKS1, echinocandin-resistant C. albicans strains with homozygous fks1 hot-spot mutations had reduced maximum catalytic capacity of their glucan synthase complexes and thicker cell walls attributable to increased cell wall chitin content. The fks1 mutants with the highest chitin contents had reduced growth rates and impaired filamentation capacities. Fks1 mutants were hypovirulent in fly and mouse models of candidiasis, and this phenotype correlated with the cell wall chitin content. In addition, we observed reduced fitness of echinocandin-resistant C. albicans in competitive mixed infection models. We conclude that fks1 mutations that confer echinocandin resistance come at fitness and virulence costs, which may limit their epidemiological and clinical impact.
Palabras clave:
Fks1
,
Echinocandin
,
Resistant
,
Virulence
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Articulos(CCT - SANTA FE)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - SANTA FE
Citación
Ben Ami, Ronen; Garcia, Guillermo Manuel; Lewis, Rusell E.; Gamarra, Maria Soledad; Leventakos, Konstantinos; et al.; Fitness and virulence costs of Candida albicans FKS1 hot spot mutations associated with echinocandin resistance; University of Chicago Press; Journal Of Infectious Diseases; 204; 4; 8-2011; 626-635
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