Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Heat shock response

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tion to pneumonia, many other fungal diseases caused wide-

spread ailments, such as moniliasis (thrush), a mouth condi-

tion that makes swallowing painful. Despite personal health

problems and stressful working conditions, Hazen persevered.

In the mid-1940s, she teamed up with Rachel Brown

(1898–1980), a chemist at the Albany laboratory who prepared

extracts from the cultures sent by Hazen. In the fall of 1950,

Hazen and Brown announced at a National Academy of

Sciences meeting that they had successfully produced two

antifungal agents from an antibiotic. This led to their develop-

ment of Nystatin, the first fungicide safe for treating humans.

Nystatin was immediately used nationwide, earning $135,000

in its first year.

Nystatin, which is still sold as a medication today under

various trade names, turned out to be an extremely versatile

substance. In addition to curing serious fungal infections of

the skin and digestive system, it can also combat Dutch Elm

disease in trees and even restore artwork damaged by water

and mold. Remarkably, Hazen and Brown chose not to accept

any royalties from the patent rights for Nystatin. Instead, they

established a foundation to support advances in science. The

donated royalties totaled more than $13 million by the time the

patent expired. Hazen died on June 24, 1975.

See alsoCandidiasis; Fungicide; Yeast, infectious

HHeat shock responseEAT SHOCK RESPONSE

The heat shock response occurs in virtually all organisms,

including bacteria. The response occurs when an environmen-

tal stress is imposed on the organism. The name of the

response comes from its discovery following the application

of a mild heat stress, only 5 to 10° C higher than the usual pre-

ferred growth temperature. However, the response, which can

be more correctly thought of as an adaptive response, consist-

ing of a temporary alteration in the metabolismof the organ-

ism, occurs in response to more than just excessive heat.

Hallmarks of the heat shock response are its rapid onset

and short-term nature. The response is an emergency coping

type of reaction to a conditions that is perceived by the organ-

ism as being threatening. The response is not a long-term com-

mitment, such as the formation of a spore by a bacterium

(although some proteins that are stimulated in the heat shock

response of Bacillus subtilisalso function in the formation of

spores by the bacteria). Rather, a heat shock response allows the

organism to cope and then to quickly resume normal function.

The alteration in the chromosome of the fruit fly

Drosophila flowing an elevation in the temperature was

reported in 1962. At the time and for some years thereafter, the

observation was regarded as an interesting curiosity that was

relevant only to the fruit fly. However, it is unequivocally

clear that the genes encoding the responsive proteins and the

structure of the proteins themselves are highly conserved in

many species. For example, three heat shock proteins that

were discovered in bacteria, which have been dubbed Hsp70,

Hsp10, and Hsp60 are highly conserved in a large number of

bacteria and in eukaryotic organisms.

Heat shock proteins are induced in large quantities in

response to factors including nutrient depletion, addition of

alcohols such as ethanol, change in the sodium concentration,

presence of heavy metals, fever, interaction with cells of a

host, and the presence of virus. The proteins are produced in

non-stress conditions. But typically their quantities are much

less. In non-stress conditions they function in the normal

metabolic events within the cell.

The heat shock response in bacteria involves the ele-

vated production of more than 20 proteins whose functions

are varied. For example, some of the proteins degrade other

proteins (proteases), while other proteins help transport mol-

ecules from one place to another while preserving their struc-

ture (these are known as chaperones). These induced proteins

act to overcome the changes that would prove destructive to

other proteins in the bacterium. By preventing protein alter-

ation and destruction, the heat shock response ensure that the

bacterium will be capable of normal function once the stress

is removed.

Some bacteria also utilize the heat shock response to

promote infection of host cells or tissue, or to survive within

host cells. Examples of bacteria include Escherichia coli,

Legionella pneumophila, and Listeria monocytogenes.

Furthermore, the alteration in structure of bacteria can involve

heat shock proteins. Examples include Bacillus subtilisspore

formation and the formation of the so-called fruiting bodies by

myxobacteria.

The principle trigger for the heat shock response in

bacteria is at the level of transcription,where the genetic

material, DNA (deoxyribonucleic acid), is used to manufac-

ture ribonucleic acid. In Escherichia colithe response is con-

trolled by what has been called a sigma factor. The sigma

factor is capable of binding to various regions of the DNA

that stimulate the transcription of the particular geneunder

their control. In other words, the single sigma factor is capa-

ble of stimulating the expression of multiple genes. The

sigma factor is under a tight and complex control, which nor-

mally restricts its activity but leaves the factor primed for

action. This is the reason for the rapid nature of the heat

shock response.

Two other heat shock response controls in bacteria

operate after the proteins are produced. These controls aid in

maintaining the proteins for a bit longer than if they were pro-

duced under non-heat shock conditions. By preserving the

structure and functions of the heat shock proteins, their activ-

ity is allowed to persist. But, once again, the protein activity

does not last indefinitely, which allows the heat shock

response to be rapidly “turned off.”

The observations that bacterial heat shock proteins can

be vital for the establishment of infections has made the heat

shock response the subject of much study, with the aim of

circumventing the response or devising vaccines that protect

host cells.

See alsoBacterial adaptation; Microbial genetics

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