Microbiology and Immunology

Penninger, Josef Martin WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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Each peptidoglycan layer of the cell wall is actually a

giant polymer molecule because all peptidoglycan chains are

cross-linked. In gram-positive bacteria there may be as many

as 40 sheets of peptidoglycan, making up to 50% of the cell

wall material. In Gram-negative bacteria, there are only one or

two sheets (about 5–10% of the cell wall material). In general,

penicillin G, or the penicillin that Fleming discovered, has

high activity against Gram-positive bacteria and low activity

against Gram-negative bacteria (with some exceptions).

Penicillin acts by inhibiting peptidoglycan synthesis by

blocking the final transpeptidation step in the synthesis of pep-

tidoglycan. It also removes the inactivator of the inhibitor of

autolytic enzymes, and the autolytic enzymes then lyses the

cell wall, and the bacterium ruptures. This latter is the final

bacteriocidal event.

Since the 1940s, many other antibiotics have been

developed. Some of these are based on the molecular structure

of penicillin; others are completely unrelated. At one time, sci-

entists assumed that bacterial infections were conquered by

the development of antibiotics. However, in the late twentieth

century, bacterial resistance to antibiotics—including peni-

cillin—was recognized as a potential threat to this success. A

classic example is the Staphylococcusbacteria, the very

species Fleming had found killed by penicillin on his Petri

dishes. By 1999, a large percentage of Staphylococcusbacte-

ria were resistant to penicillin G. Continuing research so far

has been able to keep pace with emerging resistant strains of

bacteria. Scientists and physicians must be judicious about the

use of antibiotics, however, in order to minimize bacterial

resistance and ensure that antibiotics such as penicillin remain

effective agents for treatment of bacterial infections.

See alsoAntibiotic resistance, tests for; Bacteria and bacterial

infection; Bacterial adaptation; Bacterial growth and division;

Bacterial membranes and cell wall; History of the develop-

ment of antibiotics

PPenninger, Josef MartinENNINGER, JOSEFMARTIN(1964- )

Austrian molecular immunologist

Josef Penninger is a medical doctor and molecular immunolo-

gist. In his short research career he has already made discov-

eries of fundamental significance to the understanding of

bacterial infections and heart disease, osteoporosis, and the

human immune system.

Penninger was born in Gurten, Austria. His education

was in Austria, culminating with his receipt of a M.D. and

Ph.D. from the University of Innsbruck in 1998. In 1990, he

joined the Ontario Cancer Institute in Toronto. In 1994, he

became principle investigator with the United States biotech-

nology company Amgen, joining the AMEN Research

Institute that had just been established at the Department of

Medical Biophysics at the University of Toronto.

In his decade at the AMEN Institute, Penninger has pro-

duced a steady stream of groundbreaking studies across the

breath of immunology. He and his colleagues demonstrated

that infection with the bacterial Chlamydia trachomatis

caused heart damage in mice. The basis of the damage is an

immune reaction to a bacterial protein that mimics the struc-

ture of the protein constituent of the heart valve.

As well, Penninger has shown that a protein called

CD45 is responsible for regulating how a body’s cells respond

to developmental signals, coordinates the functioning of cells

such as red and white blood cells, and regulates the response

of the immune system to viral infection. The discovery of this

key regulator and how it is co-opted in certain diseases is

already viewed as a vital step to controlling diseases and pre-

venting the immune system from attacking its own tissues (a

response called an autoimmune reaction).

The research of Penninger and others, such as Barry

Marshall and Stanley Pruisner, has caused a re-assessment of

the nature of certain diseases. Evidence is consistent so far

with a bacterial or biological origin for diseases such as schiz-

ophrenia, multiple sclerosis and Alzheimer’s disease.

Penninger already has some 150 research papers pub-

lished, many in the world’s most prestigious scientific jour-

nals. Numerous prizes and distinctions have recognized the

scope and importance of his work.

See alsoChlamydial pneumonia; Immune system

Sir Alexander Flemming, the discoverer of peniciliin.

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