Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Penicillin

427

•

then rapidly cooled to below 50°F (10°C), a temperature at

which it can then be stored. The intent of flash pasteurization

is to eliminate harmful microorganisms while maintaining the

product as close as possible to its natural state. Juices are can-

didates for this process. In milk, lactic acid bacteriacan sur-

vive. While these bacteria are not a health threat, their

subsequent metabolic activity can cause the milk to sour.

Another variation on pasteurization is known as ultra-

pasteurization. This is similar to flash pasteurization, except

that a higher than normal pressure is applied. The higher pres-

sure greatly increases the temperature that can be achieved,

and so decreases the length of time that a product, typically

milk, needs to be exposed to the heat. The advantage of ultra-

pasteurization is the extended shelf live of the milk that

results. The milk, which is essentially sterile, can be stored

unopened at room temperature for several weeks without com-

promising the quality.

In recent years the term cold pasteurization has been

used to describe the sterilizationof solids, such as food, using

radiation. The applicability of using the term pasteurization to

describe a process that does not employ heat remains a subject

of debate among microbiologists.

Pasteurization is effective only until the product is

exposed to the air. Then, microorganisms from the air can be

carried into the product and growth of microorganisms will

occur. The chance of this contaminationis lessened by storage

of milk and milk products at the appropriate storage tempera-

tures after they have been opened. For example, even ultra-pas-

teurized milk needs to stored in the refrigerator once it is in use.

See alsoBacteriocidal, bacteriostatic; Sterilization

PATHOGEN•seeMICROBIOLOGY, CLINICAL

PPenicillinENICILLIN

One of the major advances of twentieth-century medicine was

the discovery of penicillin. Penicillin is a member of the class

of drugs known as antibiotics. These drugs either kill (bacteri-

ocidal) or arrest the growth of (bacteriostatic) bacteriaand

fungi(yeast), as well as several other classes of infectious

organisms. Antibiotics are ineffective against viruses. Prior to

the advent of penicillin, bacterial infections such as pneumo-

niaand sepsis (overwhelming infection of the blood) were

usually fatal. Once the use of penicillin became widespread,

fatality rates from pneumonia dropped precipitously.

The discovery of penicillin marked the beginning of a

new era in the fight against disease. Scientists had known

since the mid-nineteenth century that bacteria were responsi-

ble for some infectious diseases, but were virtually helpless to

stop them. Then, in 1928, Alexander Fleming(1881–1955), a

Scottish bacteriologist working at St. Mary’s Hospital in

London, stumbled onto a powerful new weapon.

Fleming’s research centered on the bacteria

Staphylococcus, a class of bacteria that caused infections such

as pneumonia, abscesses, post-operative wound infections,

and sepsis. In order to study these bacteria, Fleming grew

them in his laboratory in glass Petri dishes on a substance

called agar. In August, 1928 he noticed that some of the Petri

dishes in which the bacteria were growing had become con-

taminated with mold, which he later identified as belonging to

the Penicillum family.

Fleming noted that bacteria in the vicinity of the mold

had died. Exploring further, Fleming found that the mold

killed several, but not all, types of bacteria. He also found that

an extract from the mold did not damage healthy tissue in ani-

mals. However, growing the mold and collecting even tiny

amounts of the active ingredient—penicillin—was extremely

difficult. Fleming did, however, publish his results in the med-

ical literature in 1928.

Ten years later, other researchers picked up where

Fleming had left off. Working in Oxford, England, a team led

by Howard Florey (1898–1968), an Australian, and Ernst

Chain, a refugee from Nazi Germany, came across Fleming’s

study and confirmed his findings in their laboratory. They also

had problems growing the mold and found it very difficult to

isolate the active ingredient

Another researcher on their team, Norman Heatley,

developed better production techniques, and the team was able

to produce enough penicillin to conduct tests in humans. In

1941, the team announced that penicillin could combat disease

in humans. Unfortunately, producing penicillin was still a

cumbersome process and supplies of the new drug were

extremely limited. Working in the United States, Heatley and

other scientists improved production and began making large

quantities of the drug. Owing to this success, penicillin was

available to treat wounded soldiers by the latter part of World

War II. Fleming, Florey, and Chain were awarded the Noble

Prize in medicine. Heatley received an honorary M.D. from

Oxford University in 1990.

Penicillin’s mode of action is to block the construction

of cell walls in certain bacteria. The bacteria must be repro-

ducing for penicillin to work, thus there is always some lag

time between dosage and response.

The mechanism of action of penicillin at the molecular

level is still not completely understood. It is known that the

initial step is the binding of penicillin to penicillin-binding

proteins (PBPs), which are located in the cell wall. Some PBPs

are inhibitors of cell autolytic enzymesthat literally eat the

cell wall and are most likely necessary during cell division.

Other PBPs are enzymes that are involved in the final step of

cell wall synthesis called transpeptidation. These latter

enzymes are outside the cell membrane and link cell wall com-

ponents together by joining glycopeptide polymers together to

form peptidoglycan. The bacterial cell wall owes its strength

to layers composed of peptidoglycan (also known as murein or

mucopeptide). Peptidoglycan is a complex polymer composed

of alternating N-acetylglucosamine and N-acetylmuramic acid

as a backbone off of which a set of identical tetrapeptide side

chains branch from the N-acetylmuramic acids, and a set of

identical peptide cross-bridges also branch. The tetrapeptide

side chains and the cross-bridges vary from species to species,

but the backbone is the same in all bacterial species.

womi_P 5/7/03 11:08 AM Page 427