Oxidative Stress Response Tips the Balance in Aspergillus terreus Amphotericin B Resistance.
Antimicrob Agents Chemother
; 61(10)2017 10.
Article
em En
| MEDLINE
| ID: mdl-28739793
ABSTRACT
In this study, we characterize the impact of antioxidative enzymes in amphotericin B (AmB)-resistant (ATR) and rare AmB-susceptible (ATS) clinical Aspergillus terreus isolates. We elucidate expression profiles of superoxide dismutase (SOD)- and catalase (CAT)-encoding genes, enzymatic activities of SODs, and superoxide anion production and signaling pathways involved in the oxidative stress response (OSR) in ATS and ATR strains under AmB treatment conditions. We show that ATR strains possess almost doubled basal SOD activity compared to that of ATS strains and that ATR strains exhibit an enhanced OSR, with significantly higher sod2 mRNA levels and significantly increased cat transcripts in ATR strains upon AmB treatment. In particular, inhibition of SOD and CAT proteins renders resistant isolates considerably susceptible to the drug in vitro In conclusion, this study shows that SODs and CATs are crucial for AmB resistance in A. terreus and that targeting the OSR might offer new treatment perspectives for resistant species.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aspergillus
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Superóxido Dismutase
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Catalase
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Anfotericina B
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Estresse Oxidativo
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Antifúngicos
Limite:
Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Áustria