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 > 200 μg/mL to 6.25 or 12.5 μg/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.

中文翻译：

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铁螯合剂对隐球菌物种铁相关基因的生长和表达的影响。

介绍

铁螯合剂先前已证明具有杀真菌作用。这项研究旨在调查铁螯合剂去铁胺（DFO）和地拉罗司（DSX）对隐球菌的抗真菌活性。

材料和方法

当与两性霉素B（AMB）结合使用时，使用新型隐球菌和gattii隐球菌测定DFO和DSX的最小抑菌浓度（MIC），以及DFO和DSX的抑菌浓度分数指数（FICI）。使用实时聚合酶链反应（PCR）确定隐球菌CFT1，CFT2和CIR1基因的表达。

结果

DFO和DSX均未显示出针对隐球菌菌株的抗真菌活性。当与AMB结合使用时，DFO和DSX的MIC从> 200μg/ mL降低到6.25或12.5μg/ mL。当与铁螯合剂联合使用时，大多数菌株的AMB MIC降低了1倍。DFO + AMB和DSX + AMB的FICI分别为0.5和1。当与亚MIC浓度的AMB和DFO组合孵育时，新孢梭菌显示出显着的生长迟缓；而C. gattii在DFO + AMB中表现出较小的生长迟缓。DSX与AMB结合使用时未观察到隐球菌生长迟缓。当新生隐球菌在DFO，所述生长CFT1，CFT2，和CIR1蛋白分别表达1.7、2.0和0.9倍。当新生隐球菌生长于DSX，所述CFT1，CFT2和CIR1基因表达0.5，0.6和0.3倍。

结论

在隐球菌中观察到DFO和AMB的协同抗真菌活性。CFT1和CFT2表达的相对增加可能与DFO抑制真菌生长的作用有关。