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Impact of iron chelators on growth and expression of iron-related genes of Cryptococcus species.

Abstract：

INTRODUCTION:Iron chelator has previously demonstrated fungicidal effects. This study aimed to investigate the antifungal activity of the iron chelators deferoxamine (DFO) and deferasirox (DSX) against Cryptococcus. MATERIALS AND METHODS:Cryptococcus neoformans and Cryptococcus gattii were used to determine the minimal inhibitory concentrations (MICs) of DFO and DSX, and the fractional inhibitory concentration index (FICI) of DFO and DSX when combined with amphotericin B (AMB). Expression of cryptococcal CFT1, CFT2, and CIR1 genes was determined using real-time polymerase chain reaction (PCR). RESULTS:Neither DFO nor DSX alone showed antifungal activity against Cryptococcus strains. When combined with AMB, the MICs of DFO and DSX decreased from>200μg/mL to 6.25 or 12.5μg/mL. The MIC of AMB decreased one-fold dilution in most strains when combined with iron chelators. The FICI of DFO+AMB and DSX+AMB was 0.5 and 1, respectively. C. neoformans showed significant growth retardation when incubated with a combination of sub-MIC concentrations of AMB and DFO; whereas, C. gattii demonstrated lesser growth retardation in DFO+AMB. No cryptococcal growth retardation was observed when DSX was combined with AMB. When C. neoformans was grown in DFO, the CFT1, CFT2, and CIR1 proteins were expressed 1.7, 2.0, and 0.9 times, respectively. When C. neoformans was grown in DSX, the CFT1, CFT2, and CIR1 genes were expressed 0.5, 0.6, and 0.3 times, respectively. CONCLUSION:Synergistic antifungal activity of combination DFO and AMB was observed in Cryptococcus. Relatively increased CFT1 and CFT2 expression may be associated with the effect of DFO that inhibits the growth of fungi.

journal_name

J Mycol Med

journal_title

Journal de mycologie medicale

authors

Chayakulkeeree M,Tangkoskul T,Waywa D,Tiengrim S,Pati N,Thamlikitkul V

doi

10.1016/j.mycmed.2019.100905

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

100905

issue

1

eissn

1156-5233

issn

1773-0449

pii

S1156-5233(18)30351-2

journal_volume

30

pub_type

杂志文章

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