The pathogenic yeast Cryptococcus neoformans has evolved several strategies to survive within phagocytes. Recently, it has been demonstrated that upregulation of the ATP binding cassette transporter-encoding gene antifungal resistance 1 (AFR1) is important not only for determining the resistance of C. neoformans to fluconazole but also in influencing fungal virulence. In the present study, we showed that the fluconazole-resistant AFR1-overexpressing mutant strain was not sensitive to microglia-mediated anticryptococcal activity, as compared with the fluconazole-susceptible isogenic strains, the wild type and the afr1Delta mutant. Interestingly, although the three strains were phagocytosed to a similar extent, reduced acidification and delayed maturation were observed in phagosomes containing the AFR1-overexpressing strain with respect to the others. These findings provide the first evidence that upregulation of the AFR1 gene affects C. neoformans-microglia interplay, adding insights to the complexity of cryptococcal virulence and to its unexpected link with azole resistance.

The ABC transporter-encoding gene AFR1 affects the resistance of Cryptococcus neoformans to microglia-mediated antifungal activity by delaying phagosomal maturation / Orsi, Carlotta Francesca; Colombari, Bruna; Ardizzoni, Andrea; Peppoloni, Samuele; Neglia, Rachele Giovanna; Posteraro, B; Morace, G; Fadda, G; Blasi, Elisabetta. - In: FEMS YEAST RESEARCH. - ISSN 1567-1356. - STAMPA. - 9:2(2009), pp. 301-310. [10.1111/j.1567-1364.2008.00470.x]

The ABC transporter-encoding gene AFR1 affects the resistance of Cryptococcus neoformans to microglia-mediated antifungal activity by delaying phagosomal maturation.

ORSI, Carlotta Francesca;COLOMBARI, Bruna;ARDIZZONI, Andrea;PEPPOLONI, Samuele;NEGLIA, Rachele Giovanna;BLASI, Elisabetta
2009

Abstract

The pathogenic yeast Cryptococcus neoformans has evolved several strategies to survive within phagocytes. Recently, it has been demonstrated that upregulation of the ATP binding cassette transporter-encoding gene antifungal resistance 1 (AFR1) is important not only for determining the resistance of C. neoformans to fluconazole but also in influencing fungal virulence. In the present study, we showed that the fluconazole-resistant AFR1-overexpressing mutant strain was not sensitive to microglia-mediated anticryptococcal activity, as compared with the fluconazole-susceptible isogenic strains, the wild type and the afr1Delta mutant. Interestingly, although the three strains were phagocytosed to a similar extent, reduced acidification and delayed maturation were observed in phagosomes containing the AFR1-overexpressing strain with respect to the others. These findings provide the first evidence that upregulation of the AFR1 gene affects C. neoformans-microglia interplay, adding insights to the complexity of cryptococcal virulence and to its unexpected link with azole resistance.
2009
9
2
301
310
The ABC transporter-encoding gene AFR1 affects the resistance of Cryptococcus neoformans to microglia-mediated antifungal activity by delaying phagosomal maturation / Orsi, Carlotta Francesca; Colombari, Bruna; Ardizzoni, Andrea; Peppoloni, Samuele; Neglia, Rachele Giovanna; Posteraro, B; Morace, G; Fadda, G; Blasi, Elisabetta. - In: FEMS YEAST RESEARCH. - ISSN 1567-1356. - STAMPA. - 9:2(2009), pp. 301-310. [10.1111/j.1567-1364.2008.00470.x]
Orsi, Carlotta Francesca; Colombari, Bruna; Ardizzoni, Andrea; Peppoloni, Samuele; Neglia, Rachele Giovanna; Posteraro, B; Morace, G; Fadda, G; Blasi,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/608079
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