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2017 ; 61
(11
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Novel Cell-Killing Mechanisms of Hydroxyurea and the Implication toward
Combination Therapy for the Treatment of Fungal Infections
#MMPMID28893786
Singh A
; Agarwal A
; Xu YJ
Antimicrob Agents Chemother
2017[Nov]; 61
(11
): ä PMID28893786
show ga
We have previously reported that an erg11 mutation affecting ergosterol synthesis
and a hem13 mutation in the heme synthesis pathway significantly sensitize the
fission yeast Schizosaccharomyces pombe to hydroxyurea (HU) (1, 2). Here we show
that treatment with inhibitors of Erg11 and heme biosynthesis phenocopies the two
mutations in sensitizing wild-type cells to HU. Importantly, HU synergistically
interacts with the heme biosynthesis inhibitor sampangine and several Erg11
inhibitors, the antifungal azoles, in causing cell lethality. Since the
synergistic drug interactions are also observed in the phylogenetically divergent
Saccharomyces cerevisiae and the opportunistic fungal pathogen Candida albicans,
the synergism is likely conserved in eukaryotes. Interestingly, our genetic data
for S. pombe has also led to the discovery of a robust synergism between
sampangine and the azoles in C. albicans Thus, combinations of HU, sampangine,
and the azoles can be further studied as a new method for the treatment of fungal
infections.
|Alkaloids/*pharmacology
[MESH]
|Antifungal Agents/*pharmacology
[MESH]
|Azoles/*pharmacology
[MESH]
|Candida albicans/drug effects
[MESH]
|Candidiasis/drug therapy
[MESH]
|Coproporphyrinogen Oxidase/genetics
[MESH]
|Cytochrome P-450 Enzyme System/genetics
[MESH]
|Cytokinesis/drug effects
[MESH]
|Drug Synergism
[MESH]
|Enzyme Inhibitors/*pharmacology
[MESH]
|Heterocyclic Compounds, 4 or More Rings/pharmacology
[MESH]
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