Saltar al contenido
Merck
  • The Candida albicans Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways.

The Candida albicans Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways.

PLoS pathogens (2015-10-17)
Michael Tscherner, Florian Zwolanek, Sabrina Jenull, Fritz J Sedlazeck, Andriy Petryshyn, Ingrid E Frohner, John Mavrianos, Neeraj Chauhan, Arndt von Haeseler, Karl Kuchler
RESUMEN

Human fungal pathogens like Candida albicans respond to host immune surveillance by rapidly adapting their transcriptional programs. Chromatin assembly factors are involved in the regulation of stress genes by modulating the histone density at these loci. Here, we report a novel role for the chromatin assembly-associated histone acetyltransferase complex NuB4 in regulating oxidative stress resistance, antifungal drug tolerance and virulence in C. albicans. Strikingly, depletion of the NuB4 catalytic subunit, the histone acetyltransferase Hat1, markedly increases resistance to oxidative stress and tolerance to azole antifungals. Hydrogen peroxide resistance in cells lacking Hat1 results from higher induction rates of oxidative stress gene expression, accompanied by reduced histone density as well as subsequent increased RNA polymerase recruitment. Furthermore, hat1Δ/Δ cells, despite showing growth defects in vitro, display reduced susceptibility to reactive oxygen-mediated killing by innate immune cells. Thus, clearance from infected mice is delayed although cells lacking Hat1 are severely compromised in killing the host. Interestingly, increased oxidative stress resistance and azole tolerance are phenocopied by the loss of histone chaperone complexes CAF-1 and HIR, respectively, suggesting a central role for NuB4 in the delivery of histones destined for chromatin assembly via distinct pathways. Remarkably, the oxidative stress phenotype of hat1Δ/Δ cells is a species-specific trait only found in C. albicans and members of the CTG clade. The reduced azole susceptibility appears to be conserved in a wider range of fungi. Thus, our work demonstrates how highly conserved chromatin assembly pathways can acquire new functions in pathogenic fungi during coevolution with the host.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Glicerol, ACS reagent, ≥99.5%
Sigma-Aldrich
Glicerol, for molecular biology, ≥99.0%
Sigma-Aldrich
Glicerol, ReagentPlus®, ≥99.0% (GC)
Sigma-Aldrich
Sulfato de amonio, ACS reagent, ≥99.0%
Sigma-Aldrich
Cloruro de sodio, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
Sulfato de amonio, for molecular biology, ≥99.0%
Sigma-Aldrich
Sodium chloride solution, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
Sodium chloride solution, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
Cloruro de sodio, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
Sulfato de amonio, ReagentPlus®, ≥99.0%
Sigma-Aldrich
Glicerol solution, 83.5-89.5% (T)
SAFC
Sodium chloride solution, 5 M
Sigma-Aldrich
Glicerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Glicerol, BioUltra, for molecular biology, anhydrous, ≥99.5% (GC)
Sigma-Aldrich
Sodium chloride solution, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
Cloruro de sodio, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
Glicerol, FCC, FG
Sigma-Aldrich
Cloruro de sodio, 99.999% trace metals basis
Sigma-Aldrich
Triton X-100, laboratory grade
Sigma-Aldrich
L-(−)-Glucose, ≥99%
Sigma-Aldrich
Cloruro de sodio, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
Glicerol, ≥99.5%
Sigma-Aldrich
Sulfato de amonio, BioUltra, ≥99.0% (T)
Sigma-Aldrich
Sulfato de amonio, 99.999% trace metals basis
Sigma-Aldrich
Cloruro de sodio, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
Cloruro de sodio, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
Sodium chloride solution, 5 M
Sigma-Aldrich
Glicerol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Cloruro de sodio, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Sodium chloride-35Cl, 99 atom % 35Cl