The Heat Shock Response ofMycobacterium tuberculosis: Linking Gene Expression, Immunology and Pathogenesis

The regulation of heat shock protein (HSP) expression is critically important to pathogens such asMycobacterium tuberculosisand dysregulation of the heat shock response results in increased immune recognition of the bacterium and reduced survival during chronic infection. In this study we use a whole genome spotted microarray to characterize the heat shock response ofM. tuberculosis. We also begin a dissection of this important stress response by generating deletion mutants that lack specific transcriptional regulators and examining their transcriptional profiles under different stresses. Understanding the stimuli and mechanisms that govern heat shock in mycobacteria will allow us to relate observedin vivoexpression patterns of HSPs to particular stresses and physiological conditions. The mechanisms controlling HSP expression also make attractive drug targets as part of a strategy designed to enhance immune recognition of the bacterium.

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Induction of Heat Shock Protein 70 in Mouse RPE as an In Vivo Model of Transpupillary Thermal Stimulation

International Journal of Molecular Sciences ◽

10.3390/ijms21062063 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2063

Author(s):

Mooud Amirkavei ◽

Marja Pitkänen ◽

Ossi Kaikkonen ◽

Kai Kaarniranta ◽

Helder André ◽

...

Keyword(s):

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Response ◽

Pigment Epithelium ◽

Retinal Pigment ◽

In Vivo Model ◽

Tunel Staining ◽

Long Duration ◽

Shock Response

The induction of heat shock response in the macula has been proposed as a useful therapeutic strategy for retinal neurodegenerative diseases by promoting proteostasis and enhancing protective chaperone mechanisms. We applied transpupillary 1064 nm long-duration laser heating to the mouse (C57Bl/6J) fundus to examine the heat shock response in vivo. The intensity and spatial distribution of heat shock protein (HSP) 70 expression along with the concomitant probability for damage were measured 24 h after laser irradiation in the mouse retinal pigment epithelium (RPE) as a function of laser power. Our results show that the range of heating powers for producing heat shock response while avoiding damage in the mouse RPE is narrow. At powers of 64 and 70 mW, HSP70 immunostaining indicates 90 and 100% probability for clearly elevated HSP expression while the corresponding probability for damage is 20 and 33%, respectively. Tunel staining identified the apoptotic regions, and the estimated 50% damaging threshold probability for the heating (ED50) was ~72 mW. The staining with Bestrophin1 (BEST1) demonstrated RPE cell atrophy with the most intense powers. Consequently, fundus heating with a long-duration laser provides an approachable method to develop heat shock-based therapies for the RPE of retinal disease model mice.

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In vivo heat-shock response in the brain: signalling pathway and transcription factor activation

Molecular Brain Research ◽

10.1016/j.molbrainres.2003.08.018 ◽

2003 ◽

Vol 119 (1) ◽

pp. 90-99 ◽

Cited By ~ 32

Author(s):

Paola Maroni ◽

Paola Bendinelli ◽

Laura Tiberio ◽

Francesca Rovetta ◽

Roberta Piccoletti ◽

...

Keyword(s):

Transcription Factor ◽

Heat Shock ◽

Heat Shock Response ◽

Signalling Pathway ◽

Transcription Factor Activation ◽

Shock Response ◽

The Brain

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Global Gene Expression Analysis of the Heat Shock Response in the Phytopathogen Xylella fastidiosa

Journal of Bacteriology ◽

10.1128/jb.00182-06 ◽

2006 ◽

Vol 188 (16) ◽

pp. 5821-5830 ◽

Cited By ~ 23

Author(s):

Tie Koide ◽

Ricardo Z. N. Vêncio ◽

Suely L. Gomes

Keyword(s):

Heat Shock ◽

Stress Responses ◽

Heat Shock Response ◽

Time Course ◽

Protein Biosynthesis ◽

Xylella Fastidiosa ◽

Expression Profiles ◽

Expression Patterns ◽

Phytopathogenic Bacterium ◽

Shock Response

ABSTRACT Xylella fastidiosa is a phytopathogenic bacterium that is responsible for diseases in many economically important crops. Although different strains have been studied, little is known about X. fastidiosa stress responses. One of the better characterized stress responses in bacteria is the heat shock response, which induces the expression of specific genes to prevent protein misfolding and aggregation and to promote degradation of the irreversibly denatured polypeptides. To investigate X. fastidiosa genes involved in the heat shock response, we performed a whole-genome microarray analysis in a time course experiment. Globally, 261 genes were induced (9.7%) and 222 genes were repressed (8.3%). The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated by quantitative reverse transcription-PCR experiments. We determined the transcription start sites of six heat shock-inducible genes and analyzed their promoter regions, which allowed us to propose a putative consensus for σ32 promoters in Xylella and to suggest additional genes as putative members of this regulon. Besides the induction of classical heat shock protein genes, we observed the up-regulation of virulence-associated genes such as vapD and of genes for hemagglutinins, hemolysin, and xylan-degrading enzymes, which may indicate the importance of heat stress to bacterial pathogenesis. In addition, we observed the repression of genes related to fimbriae, aerobic respiration, and protein biosynthesis and the induction of genes related to the extracytoplasmic stress response and some phage-related genes, revealing the complex network of genes that work together in response to heat shock.

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HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models

Scientific Reports ◽

10.1038/s41598-017-12897-0 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 8

Author(s):

Andreas Neueder ◽

Theresa A. Gipson ◽

Sophie Batterton ◽

Hayley J. Lazell ◽

Pamela P. Farshim ◽

...

Keyword(s):

Heat Shock ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Mouse Models ◽

Heat Shock Response ◽

Shock Response

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Global Gene Expression Profiles of the Cyanobacterium Synechocystis sp. Strain PCC 6803 in Response to Irradiation with UV-B and White Light

Journal of Bacteriology ◽

10.1128/jb.184.24.6845-6858.2002 ◽

2002 ◽

Vol 184 (24) ◽

pp. 6845-6858 ◽

Cited By ~ 137

Author(s):

Lixuan Huang ◽

Michael P. McCluskey ◽

Hao Ni ◽

Robert A. LaRossa

Keyword(s):

Gene Expression ◽

Heat Shock ◽

White Light ◽

Heat Shock Response ◽

High Intensity ◽

Expression Profiles ◽

Expression Patterns ◽

Stringent Response ◽

Shock Response ◽

Pcc 6803

ABSTRACT We developed a transcript profiling methodology to elucidate expression patterns of the cyanobacterium Synechocystis sp. strain PCC 6803 and used the technology to investigate changes in gene expression caused by irradiation with either intermediate-wavelength UV light (UV-B) or high-intensity white light. Several families of transcripts were altered by UV-B treatment, including mRNAs specifying proteins involved in light harvesting, photosynthesis, photoprotection, and the heat shock response. In addition, UV-B light induced the stringent response in Synechocystis, as indicated by the repression of ribosomal protein transcripts and other mRNAs involved in translation. High-intensity white light- and UV-B-mediated expression profiles overlapped in the down-regulation of photosynthesis genes and induction of heat shock response but differed in several other transcriptional processes including those specifying carbon dioxide uptake and fixation, the stringent response, and the induction profile of the high-light-inducible proteins. These two profile comparisons not only corroborated known physiological changes but also suggested coordinated regulation of many pathways, including synchronized induction of D1 protein recycling and a coupling between decreased phycobilisome biosynthesis and increased phycobilisome degradation. Overall, the gene expression profile analysis generated new insights into the integrated network of genes that adapts rapidly to different wavelengths and intensities of light.

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Heat-shock protein expression is absent in the antarctic fish Trematomus bernacchii (family Nototheniidae)

Journal of Experimental Biology ◽

10.1242/jeb.203.15.2331 ◽

2000 ◽

Vol 203 (15) ◽

pp. 2331-2339 ◽

Cited By ~ 19

Author(s):

G.E. Hofmann ◽

B.A. Buckley ◽

S. Airaksinen ◽

J.E. Keen ◽

G.N. Somero

Keyword(s):

Protein Synthesis ◽

Heat Shock ◽

Heat Shock Protein ◽

Heat Shock Response ◽

Solid Phase ◽

Antarctic Fish ◽

Shock Response ◽

Enhanced Expression ◽

Trematomus Bernacchii

The heat-shock response, the enhanced expression of one or more classes of molecular chaperones termed heat-shock proteins (hsps) in response to stress induced by high temperatures, is commonly viewed as a ‘universal’ characteristic of organisms. We examined the occurrence of the heat-shock response in a highly cold-adapted, stenothermal Antarctic teleost fish, Trematomus bernacchii, to determine whether this response has persisted in a lineage that has encountered very low and stable temperatures for at least the past 14–25 million years. The patterns of protein synthesis observed in in vivo metabolic labelling experiments that involved injection of (35)S-labelled methionine and cysteine into whole fish previously subjected to a heat stress of 10 degrees C yielded no evidence for synthesis of any size class of heat-shock protein. Parallel in vivo labelling experiments with isolated hepatocytes similarly showed significant amounts of protein synthesis, but no indication of enhanced expression of any class of hsp. The heavy metal cadmium, which is known to induce synthesis of hsps, also failed to alter the pattern of proteins synthesized in hepatocytes. Although stress-induced chaperones could not be detected under any of the experimental condition used, solid-phase antibody (western) analysis revealed that a constitutively expressed 70 kDa chaperone was present in this species, as predicted on the basis of requirements for chaperoning during protein synthesis. Amounts of the constitutively expressed 70 kDa chaperone increased in brain, but not in gill, during 22 days of acclimation to 5 degrees C. The apparent absence of a heat-shock response in this highly stenothermal species is interpreted as an indication that a physiological capacity observed in almost all other organisms has been lost as a result of the absence of positive selection during evolution at stable sub-zero temperatures. Whether the loss of the heat-shock response is due to dysfunctional genes for inducible hsps (loss of open reading frames or functional regulatory regions), unstable messenger RNAs, the absence of a functional heat-shock factor or some other lesion remains to be determined.

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Genetic differences in the duration of the lymphocyte heat shock response in mice.

Genetics ◽

10.1093/genetics/124.4.949 ◽

1990 ◽

Vol 124 (4) ◽

pp. 949-955

Author(s):

V K Mohl ◽

G D Bennett ◽

R H Finnell

Keyword(s):

Protein Synthesis ◽

Heat Shock ◽

Heat Shock Response ◽

Mouse Strains ◽

Adult Mice ◽

Shock Response ◽

Increased Sensitivity ◽

Shock Proteins ◽

The Relationship

Abstract Lymphocytes from adult mice bearing a known difference in genetic susceptibility to teratogen-induced exencephaly (SWV/SD, and DBA/2J) were evaluated for changes in protein synthesis following an in vivo heat treatment. Particular attention was paid to changes indicative of the heat shock response, a highly conserved response to environmental insult consisting of induction of a few, highly conserved proteins with simultaneous decreases in normal protein synthesis. The duration of heat shock protein induction in lymphocytes was found to be increased by 1 hr in the teratogen-sensitive SWV/SD strain as compared to the resistant DBA/2J strain. Densitometric analysis revealed a significant decrease in the relative synthesis of at least two non-heat shock proteins (36 kD and 45 kD) in the SWV/SD lymphocytes as compared to DBA/2J cells. The increased sensitivity of protein synthesis to hyperthermia in the SWV/SD lymphocytes were lost in the F1 progeny of reciprocal crosses between SWV/SD and DBA/2J mouse strains. Sensitivity to hyperthermia-induced exencephaly is recessive to resistance in these crosses. The relationship between altered protein synthesis and teratogen susceptibility is discussed.

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