A Dereeper

A Hartl

A Hubel

A Shonhai

A Walther

A Yamamoto

AA Sanchez

AF Ram

AJ Brown

AJP Brown

Alistair J. P. Brown

AM Gillum

AM Murad

B Eisman

B Enjalbert

B Hube

B Wachtler

Bernhard Hube

C Askew

C Csank

C Fradin

C Gancedo

C Schuller

CA Kumamoto

CC Sheth

CF Urban

CJ Nobile

D Harcus

D Ribatti

DA Smith

DL Richie

DM Arana

Duncan Wilson

E Roman

EA Craig

F Estruch

F Moller

F Narberhaus

FA Castro

FC Odds

FJ Alvarez-Peral

François L. Mayer

G Butler

GJ Caspers

GR Stewart

H Liu

H Park

H Ruis

H Wisplinghoff

H Yamaguchi

HJ Lo

HT Rupniak

ID Jacobsen

Ilse D. Jacobsen

Iryna M. Bohovych

J Buchner

J Fan

J Ferrer

J Horwitz

JC Arguelles

JD Malhotra

JN Sun

JP Burnie

JR Glover

K Richter

K Sales

K Zakikhany

KD Metzler

KL Meibom

L Petko

LE Cowen

LL Hoyer

LY Chiang

M Chaput

M Haslbeck

M Lis

M Martinez-Esparza

M Ramsdale

M Ruhnke

M Werner-Washburne

MA Ramirez

MC Lorenz

MG Marcu

N Benaroudj

N Jaya

N Santoro

NA Gow

Neeraj Chauhan

O Zaragoza

P Ratnakar

P Van Dijck

PLoS ONE

English

PubMed

<div>Small heat shock proteins (sHsps) have multiple cellular functions. However, the biological function of sHsps in pathogenic microorganisms is largely unknown. In the present study we identified and characterized the novel sHsp Hsp21 of the human fungal pathogen Candida albicans. Using a reverse genetics approach we demonstrate the importance of Hsp21 for resistance of C. albicans to specific stresses, including thermal and oxidative stress. Furthermore, a hsp21Δ/Δ mutant was defective in invasive growth and formed significantly shorter filaments compared to the wild type under various filament-inducing conditions. Although adhesion to and invasion into human-derived endothelial and oral epithelial cells was unaltered, the hsp21Δ/Δ mutant exhibited a strongly reduced capacity to damage both cell lines. Furthermore, Hsp21 was required for resisting killing by human neutrophils. Measurements of intracellular levels of stress protective molecules demonstrated that Hsp21 is involved in both glycerol and glycogen regulation and plays a major role in trehalose homeostasis in response to elevated temperatures. Mutants defective in trehalose and, to a lesser extent, glycerol synthesis phenocopied HSP21 deletion in terms of increased susceptibility to environmental stress, strongly impaired capacity to damage epithelial cells and increased sensitivity to the killing activities of human primary neutrophils. Via systematic analysis of the three main C. albicans stress-responsive kinases (Mkc1, Cek1, Hog1) under a range of stressors, we demonstrate Hsp21-dependent phosphorylation of Cek1 in response to elevated temperatures. Finally, the hsp21Δ/Δ mutant displayed strongly attenuated virulence in two in vivo infection models. Taken together, Hsp21 mediates adaptation to specific stresses via fine-tuning homeostasis of compatible solutes and activation of the Cek1 pathway, and is crucial for multiple stages of C. albicans pathogenicity. Hsp21 therefore represents the first reported example of a small heat shock protein functioning as a virulence factor in a eukaryotic pathogen. </div

François L. Mayer (159482)

Duncan Wilson (155296)

Ilse D. Jacobsen (149635)

Pedro Miramón (108557)

Silvia Slesiona (159490)

Iryna M. Bohovych (108563)

Alistair J. P. Brown (108565)

Bernhard Hube (108571)

The Francis Crick Institute

Small but Crucial: The Novel Small Heat Shock Protein Hsp21 Mediates Stress Adaptation and Virulence in Candida albicans

Mayer, François L

Wilson, Duncan

Jacobsen, Ilse D

Miramón, Pedro

Slesiona, Silvia

Bohovych, Iryna M

Brown, Alistair J P

Hube, Bernhard

Aberdeen University Research

[The Candida infected hen’s egg. An alternative test system for systemic anticandida activity].

A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans.

A contact-activated kinase signals Candida albicans invasive growth and biofilm development.

A newly discovered protein export machine in malaria parasites.

A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus.

Alpha-crystallin-type heat shock proteins: socializing minichaperones in the context of a multichaperone network. Microbiol Mol Biol Rev 66: 64–93; table of contents.

Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.

An enzymatic, spectrophotometric glycerol assay with increased basic sensitivity.

An improved transformation protocol for the human fungal pathogen Candida albicans.

An RNA transport system in Candida albicans regulates hyphal morphology and invasive growth.

Antimicrobial peptide MUC7 12-mer activates the calcium/calcineurin pathway in Candida albicans.

Candida albicans HSP12 is co-regulated by physiological CO2 and pH.

Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis.

Candida albicans proteinases: resolving the mystery of a gene family. Microbiology 147: 1997–2005.

Candida albicans transcription factor Rim101 mediates pathogenic interactions through cell wall functions.

Candida and Candidiasis.

Candida infections: an overview.

Catanzaro A

Characteristics of four new human cell lines derived from squamous cell carcinomas of the head and neck.

Chemical chaperones regulate molecular chaperones in vitro and in cells under combined salt and heat stresses.

Chorioallantoic membrane capillary bed: a useful target for studying angiogenesis and antiangiogenesis in vivo.

CIp10, an efficient and convenient integrating vector for Candida albicans.

Complex interactions among members of an essential subfamily of hsp70 genes in Saccharomyces cerevisiae.

Cytotoxicity mechanism of two naphthoquinones (menadione and plumbagin) in Saccharomyces cerevisiae.

Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress.

Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans.

Disassembling protein aggregates in the yeast cytosol.

Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family–a sticky pursuit.

Disruption in Candida albicans of the TPS2 gene encoding trehalose-6-phosphate phosphatase affects cell integrity and decreases infectivity.

Disruption of a gene encoding glycerol 3-phosphatase from Candida albicans impairs intracellular glycerol accumulation-mediated salt-tolerance.

Disruption of the Candida albicans TPS1 gene encoding trehalose-6-phosphate synthase impairs formation of hyphae and decreases infectivity.

Disruption of the Candida albicans TPS2 gene encoding trehalose-6-phosphate phosphatase decreases infectivity without affecting hypha formation.

Embryonated eggs as an alternative infection model to investigate Aspergillus fumigatus virulence.

Essential roles of 70kDa heat inducible proteins.

Evolution of pathogenicity and sexual reproduction in eight Candida genomes.

Flow cytometric analysis of the heat shock protein 60 expressed on the cell surface of Helicobacter pylori.

From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells.

Fungal heat-shock proteins in human disease.

Fungal morphogenesis and host invasion.

Fungal morphogenesis: some like it hot.

Genome-wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress.

Glycoconjugate expression on the cell wall of tps1/tps1 trehalose-deficient Candida albicans strain and implications for its interaction with macrophages.

Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood.

Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease.

Heat shock element architecture is an important determinant in the temperature and transactivation domain requirements for heat shock transcription factor.

Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alpha.

Heat-shock proteins and pathogenesis of bacterial infections.

Heat-shock proteins and stress tolerance in microorganisms.

Heritable glycogen-storage deficiency in yeast and its induction by ultra-violet light.

Host cell invasion and virulence mediated by Candida albicans

Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins.

Hsp12 is an intrinsically unstructured stress protein that folds upon membrane association and modulates membrane function.

Hsp26 is not required for growth at high temperatures, nor for thermotolerance, spore development, or germination.

Hsp26: a temperature-regulated chaperone.

Hsp30, the integral plasma membrane heat shock protein of Saccharomyces cerevisiae, is a stress-inducible regulator of plasma membrane H(+)-ATPase.

Hsp42 is the general small heat shock protein in the cytosol of Saccharomyces cerevisiae.

Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling.

Identification of a novel class of target genes and a novel type of binding sequence of heat shock transcription factor in Saccharomyces cerevisiae.

Identification of fungal cell wall mutants using susceptibility assays based on Calcofluor white and Congo red.

Immunopathogenesis of recurrent vulvovaginal candidiasis.

In vivo and ex vivo comparative transcriptional profiling of invasive and non-invasive Candida albicans isolates identifies genes associated with tissue invasion.

In vivo transcript profiling of Candida albicans identifies a gene essential for interepithelial dissemination.

Integration of metabolism with virulence in Candida albicans.

Isolation of the Candida albicans gene for orotidine-5’-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations.

Kullberg BJ (2002) Deep-seated candidal infections.

Leishmania major Hsp100 is required chiefly in the mammalian stage of the parasite.

MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans.M o l

Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes.

Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity.

Nature’s molecular sponges: small heat shock proteins grow into their chaperone roles.

Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.

New modules for PCR-based gene targeting in Candida albicans: rapid and efficient gene targeting using 100 bp of flanking homology region.

Nitrosative and oxidative stress responses in fungal pathogenicity.

Nonfilamentous C. albicans mutants are avirulent.

Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.

Osmotic stress signaling and osmoadaptation in yeasts.

Pathogenesis of Candida albicans infections in the alternative chorio-allantoic membrane chicken embryo model resembles systemic murine infections.

Phylogeny.fr: robust phylogenetic analysis for the non-specialist.

Plasmodial heat shock proteins: targets for chemotherapy.

Protective role of trehalose during severe oxidative stress caused by hydrogen peroxide and the adaptive oxidative stress response in Candida albicans.

Purification and characterization of a heatshock element binding protein from yeast.

Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions.

Ras1 and Ras2 play antagonistic roles in regulating cellular cAMP level, stationary-phase entry and stress response in Candida albicans.

Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro.

Role of hyphal formation in interactions of Candida albicans with endothelial cells.

Role of the fungal Ras-protein kinase A pathway in governing epithelial cell interactions during oropharyngeal candidiasis.

Role of the heat shock transcription factor, Hsf1, in a major fungal pathogen that is obligately associated with warm-blooded animals.

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

https://figshare.com/articles/Small_but_Crucial_The_Novel_Small_Heat_Shock_Protein_Hsp21_Mediates_Stress_Adaptation_and_Virulence_in_Candida_albicans_/124157

Small but crucial : the novel small heat shock protein Hsp21 mediates stress adaptation and virulence in Candida albicans

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