Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Cohen, Stanley N.

125

•

CCoagulaseOAGULASE

Coagulase is an enzyme that is produced by some types of

bacteria. The enzyme clots the plasma component of the

blood. The only significant disease-causing bacteria of

humans that produces coagulase is Staphylococcus aureus.

In the human host, the action of coagulase produces

clotting of the plasma in the immediate vicinity of the bac-

terium. The resulting increased effective diameter of the bac-

terium makes it difficult for the defense reactions of the host

to deal with the infecting cell. In particular, the defensive

mechanism of phagocytosis, where the bacterium is engulfed

by a host cell and then dissolved, is rendered ineffective. This

enables the bacterium to persist in the presence of a host

immune response, which can lead to the establishment of n

infection. Thus, coagulase can be described as a disease-caus-

ing (or virulence) factor of Staphylococcus aureus

A test for the presence of active coagulase distin-

guishes the aureus Staphylococcus from the non-aureus

Staphylococci. Staphylococcus aureusis one of the major

causes of hospital-acquired infection. Antibiotic resistance

of this strain is a major concern. In the non-aureus, coagu-

lase-negative group, Staphylococcus epidermidisis a partic-

ular concern. This strain is also an important disease-causing

organism in hospital settings and can establish infections on

artificial devices inserted into the body. The ability to

quickly and simply differentiate the two different types of

Staphylococcusfrom each other enables the proper treatment

to be started before the infections become worse.

In the test, the sample is added to rabbit plasma and held

at 37° C or a specified period of time, usually bout 12 hours.

A positive test is the formation of a visible clump, which is the

clotted plasma. Samples must be observed for clotting within

24 hours. This is because some strains that produce coagulase

also produce an enzyme called fibrinolysin, which can dis-

solve the clot. Therefore, the absence of a clot after 24 hours

is no guarantee that a clot never formed. The formation of a

clot by 12 hours and the subsequent disappearance of the clot

by 24 hours could produce a so-called false negative if the test

were only observed at the 24-hour time.

See alsoBiochemical analysis techniques; Laboratory tech-

niques in microbiology

CCohen, Stanley N.OHEN, STANLEYN.(1935- )

American geneticist

Modern biology, biochemistry, and genetics were fundamen-

tally changed in 1973 when Stanley N. Cohen, Herbert W.

Boyer, Annie C. Y. Chang, and Robert B. Helling developed a

technique for transferring DNA, the molecular basis of hered-

ity, between unrelated species. Not only was DNA propaga-

tion made possible among different bacterial species, but

successful geneinsertion from animal cells into bacterial cells

was also accomplished. Their discovery, called recombinant

DNA or genetic engineering, introduced the world to the age

of modern biotechnology.

As with any revolutionary discovery, the benefits of this

new technology were both immediate and projected.

Immediate gains were made in the advancement of fundamen-

tal biology by increasing scientists’ knowledge of gene struc-

ture and function. This knowledge promised new ways to

overcome disease, increase food production, and preserve

renewable resources. For example, the use of recombinant

DNA methodology to overcome antibiotic resistanceon the

part of bacteriaanticipated the development of better vac-

cines. A new source for producing insulin and other life-sus-

taining drugs had the potential to be realized. And, by creating

new, nitrogen-fixing organisms, it was thought that food pro-

duction could be increased, and the use of expensive, environ-

mentally harmful nitrogen fertilizers eliminated. Genetic

engineering also offered the promise of nonpolluting energy

sources, such as hydrogen-producing algae. In the decades fol-

lowing the discovery of the means for propagating DNA,

many assumptions regarding the benefits of genetic engineer-

ing have proved to be viable, and the inventions and technol-

ogy that were by-products of genetic engineering research

became marketable commodities, propelling biotechnology

into a dynamic new industry.

Stanley N. Cohen was born in Perth Amboy, New

Jersey, to Bernard and Ida Stolz Cohen. He received his under-

graduate education at Rutgers University, and his M.D. degree

from the University of Pennsylvania in 1960. Then followed

medical positions at Mt. Sinai Hospital in New York City,

University Hospital in Ann Arbor, Michigan, the National

Institute for Arthritis and Metabolic Diseases in Bethesda,

Maryland, and Duke University Hospital in Durham, North

Carolina. Cohen completed postdoctoral research in 1967 at

the Albert Einstein College of Medicine in the Bronx, New

York. He joined the faculty at Stanford University in 1968,

was appointed professor of medicine in 1975, professor of

genetics in 1977, and became Kwoh-Ting Li professor of

genetics in 1993.

At Stanford Cohen began the study of plasmids—bits

of DNA that exist apart from the genetic information-carrying

chromosomes—to determine the structure and function of

plasmid genes. Unlike species ordinarily do not exchange

genetic information. But Cohen found that the independent

plasmidshad the ability to transfer DNA to a related-species

cell, though the phenomenon was not a commonplace occur-

rence. In 1973 Cohen and his colleagues successfully

achieved a DNA transfer between two different sources.

These functional molecules were made by joining two differ-

ent plasmid segments taken from Escherichia coli,a bacteria

found in the colon, and inserting the combined plasmid DNA

back into E. colicells. They found that the DNA would repli-

cate itself and express the genetic information contained in

each original plasmid segment. Next, the group tried this

experiment with an unrelated bacteria, Staphylococcus. This,

too, showed that the original Staphylococcusplasmid genes

would transfer their biological properties into the E. colihost.

With this experiment, the DNA barrier between species was

broken. The second attempt at DNA replication between

unlike species was that of animal to bacteria. This was suc-

cessfully undertaken with the insertion into E. coliof genes

womi_C 5/6/03 2:04 PM Page 125