Heat Shock Response during Morphogenesis in the Dimorphic Pathogenic Fungus Histoplasma capsulatum

Changes in temperature and a variety of other stimuli coordinately induce transcription of a specific set of heat-shock genes in all organisms. In the human fungal pathogen Histoplasma capsulatum, a temperature shift from 25 to 37 °C acts not only as a signal that causes transcription of heat-shock genes, but also triggers a morphological mycelium-to yeast-phase transition. The temperature-induced morphological transition may be viewed as a heat-shock response followed by cellular adaptation to a higher temperature. We have found that by inducing thermotolerance, i.e., an initial incubation at 34 °C, the thermosensitive attenuated Downs strain of H. capsulatum can be made to resemble those of the more temperature-tolerant G222B strain with respect to mitochondrial ATPase activity and electron transport efficiency at elevated temperatures. Furthermore, if the heat-shock response is first elicited by preincubation at milder temperatures or stress, transcription of heat-shock mRNA in mycelial cells of Downs strain that shifted to 37 °C proceeds at rates comparable to those of the virulent strains.Key words: heat shock, thermotolerance, ATPase, 70-kilodalton heat-shock protein, fungal morphogenesis.

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Possible relationship of morphogenesis in pathogenic fungus, Histoplasma capsulatum, to heat shock response

Nature ◽

10.1038/303806a0 ◽

1983 ◽

Vol 303 (5920) ◽

pp. 806-808 ◽

Cited By ~ 47

Author(s):

Alan M. Lambowitz ◽

George S. Kobayashi ◽

Audrey Painter ◽

Gerald Medoff

Keyword(s):

Heat Shock ◽

Heat Shock Response ◽

Histoplasma Capsulatum ◽

Pathogenic Fungus ◽

Shock Response ◽

Relationship Of

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Changes in Membrane Fluid State and Heat Shock Response Cause Attenuation of Virulence

Journal of Bacteriology ◽

10.1128/jb.00990-09 ◽

2010 ◽

Vol 192 (7) ◽

pp. 1999-2005 ◽

Cited By ~ 11

Author(s):

Amalia Porta ◽

Annamaria Eletto ◽

Zsolt Török ◽

Silvia Franceschelli ◽

Attila Glatz ◽

...

Keyword(s):

Heat Shock ◽

Genetic Modification ◽

Heat Shock Response ◽

Mammalian Cells ◽

Histoplasma Capsulatum ◽

Genetic Manipulation ◽

Microbial Pathogens ◽

Fluid State ◽

Shock Response ◽

Serovar Typhimurium

ABSTRACT So far attenuation of pathogens has been mainly obtained by chemical or heat treatment of microbial pathogens. Recently, live attenuated strains have been produced by genetic modification. We have previously demonstrated that in several prokaryotes as well as in yeasts and mammalian cells the heat shock response is controlled by the membrane physical state (MPS). We have also shown that in Salmonella enterica serovar Typhimurium LT2 (Salmonella Typhimurium) overexpression of a Δ12-desaturase gene alters the MPS, inducing a sharp impairment of transcription of major heat shock genes and failure of the pathogen to grow inside macrophage (MΦ) (A. Porta et al., J. Bacteriol. 192:1988-1998, 2010). Here, we show that overexpression of a homologous Δ9-desaturase sequence in the highly virulent G217B strain of the human fungal pathogen Histoplasma capsulatum causes loss of its ability to survive and persist within murine MΦ along with the impairment of the heat shock response. When the attenuated strain of H. capsulatum was injected in a mouse model of infection, it did not cause disease. Further, treated mice were protected when challenged with the virulent fungal parental strain. Attenuation of virulence in MΦ of two evolutionarily distant pathogens was obtained by genetic modification of the MPS, suggesting that this is a new method that may be used to produce attenuation or loss of virulence in both other intracellular prokaryotic and eukaryotic pathogens. This new procedure to generate attenuated forms of pathogens may be used eventually to produce a novel class of vaccines based on the genetic manipulation of a pathogen's membrane fluid state and stress response.

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Heat-shock response in Fonsecaea pedrosoi, a pathogenic fungus

Canadian Journal of Microbiology ◽

10.1139/m92-212 ◽

1992 ◽

Vol 38 (12) ◽

pp. 1286-1291 ◽

Cited By ~ 3

Author(s):

Christine Laurent-Winter ◽

Oumaima Ibrahim-Granet

Keyword(s):

Heat Shock ◽

Heat Shock Proteins ◽

Heat Shock Response ◽

Pathogenic Fungus ◽

Heat Stroke ◽

Two Dimensional ◽

Fonsecaea Pedrosoi ◽

Shock Response ◽

Shock Proteins ◽

Dimensional Electrophoresis

Using two-dimensional electrophoresis we have investigated the heat-shock response in a pathogenic fungus, Fonsecaea pedrosoi. Fungal cultures were transferred from 37 to 45 °C for either 30 or 90 min and then returned back to the initial temperature. Analysis of the total proteins resolved on two-dimensional gels indicated important changes in the accumulation of several peptides according to the duration of treatment and the temperature. The 30-min incubation at 45 °C resulted in the induction of several new proteins, whereas other proteins were either increased or decreased. These inductions and repressions of proteins (called heat-shock and heat-stroke proteins, respectively) were either specific to this time period or still present after a 90-min incubation. In addition, the 90-min incubation period led to the enhancement of several proteins, which were therefore called late heat-shock proteins to distinguish them from the early ones detected after 30 min. Finally, when cultures were shifted back to 37 °C most of the heat-shock proteins decreased or disappeared; in parallel, most of the heat-stroke proteins were reinduced at this time. These results are in good agreement with previous studies on the heat-shock response and provide additional evidence that this phenomenon is highly conserved among species. Key words: heat-shock proteins, two-dimensional electrophoresis, pathogenic fungus, Fonsecaea pedrosoi.

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