Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis

被引：48

作者：

Lamoth, Frederic ^{[1
,2
,3
]}

Juvvadi, Praveen R. ^{[1
]}

Steinbach, William J. ^{[1
,4
]}

机构：

[1] Duke Univ, Med Ctr, Dept Pediat, Div Pediat Infect Dis, Durham, NC 27710 USA

[2] Univ Lausanne Hosp, Dept Med, Infect Dis Serv, Lausanne, Switzerland

[3] Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland

[4] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

来源：

FRONTIERS IN MICROBIOLOGY | 2015年 / 6卷

基金：

瑞士国家科学基金会;

关键词：

lysine deacetylases; Aspergillus fumigatus; trichostatin A; heat shock protein 90; antifungal therapy; antifungal resistance; SHOCK-PROTEIN; 90; SUBEROYLANILIDE HYDROXAMIC ACID; PROTEASOMAL DEGRADATION; LYSINE ACETYLATION; DRUG-RESISTANCE; TRICHOSTATIN-A; HSP90; FUNCTION; GROWTH; VORINOSTAT; EXPRESSION;

D O I：

10.3389/fmicb.2015.00096

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.

引用

页数：6

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