Soil is commonly used in antibiotics. Microbes created in
the soil are harmful to bacteria, which is why soil is used in medicine.
Medicines created by soil include skin ointments, tuberculosis drugs
and anti-tumor drugs.
While many people recognize the important duties that soil performs in
our everyday lives—nourishing plants, filtering ground and surface water
and providing a foundation for our homes and offices—most do not realize
that soil has also served as an important source of commonly used
antibiotics.
Soil is indeed almost a perfect laboratory for the creation of natural
medicines. Soil contains a wide array of tiny microhabitats that creates
an enormous variation in the appearance and survival strategies of soil
microbes. This diverse group of microbes, of which there are billions in
an average teaspoon of soil, must then compete with one another for every
available nourishing piece of organic matter. Through the lens of a
microscope, scientists have observed this fracas and realized that the
methods microbes use to subdue other microbes in the soil can be adapted
to fight infections in the human body.
The pioneering work behind the discovery of soil-derived antibiotics was
performed by Dr. Selman Waksman. In fact, it was Dr. Waksman who coined
the term antibiotic to describe the focus of his research. Dr. Waksman
was a Russian immigrant who came to the United States in 1911 to study
agriculture at Rutgers University. After receiving a Ph.D. in
biochemistry from the University of California and becoming a naturalized
citizen, he returned to Rutgers to become a lecturer of soil microbiology
and a microbiologist at the New Jersey Agricultural Experiment Station.
He later became a full professor and used his position to study an order
of soil bacteria called the actinomycetes. Actinomycetes seemed to
compete for food in the soil by secreting compounds that were harmful to
rival bacteria, thus keeping them away. Dr. Waksman realized that if he
could identify and isolate these compounds, he might be able to use them
to combat human infections.
Indeed, starting with the discovery of actinomycin in 1940 until his
retirement in 1958, Dr. Waksman and his students derived 22 different
antibiotic compounds from actinomycetes. Three of the antibiotics —
actinomycin, neomycin and streptomycin — became commonly used.
Actinomycin, the first antibiotic isolated by Dr. Waksman, is used
sparingly as an anti-tumor drug (it is highly toxic) and frequently as an
investigative tool for cell biologists. Neomycin is an extremely common
antibiotic that is found in many skin ointments such as Neosporin®, as
well as numerous treatments for eye and ear infections. Streptomycin was
the first practical treatment for tuberculosis.
While working at Rutgers, Dr. Waksman was also hired as a consultant to
the Merck pharmaceutical company. A share of the royalties from patents
held by Merck on Waksman’s antibiotics and other medicines went back to
Rutgers University and helped to establish a fellowship in the Department
of Soils. Dr. Waksman convinced Merck to license out streptomycin to
other manufacturers and used the profits to found the Institute of
Microbiology at Rutgers, which was renamed the Waksman Institute of
Microbiology after his death. As a result of his work and charity, Dr.
Waksman was awarded the Nobel Prize in 1952. He is the only soil
scientist ever to have received that honor.
Looking to the soil for antibiotics did not stop with Dr. Waksman’s
retirement. Vancomycin, an antibiotic isolated in 1956 from a species of
actinomycete found in Indian and Indonesian soils, is extremely powerful
and the current last line of defense for the treatment of bacterial
infections. However, as with all other antibiotics, strains of bacteria
resistant to vancomycin recently have been discovered. This means that
some bacteria are now impervious to all known treatments. This is a scary
reality, but rest assured that scientists are already at work in the
soil, trying to find the microbe that will provide the next miracle
medicine.
Erythromycin is a
macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of
penicillin, and is often
prescribed for people who have an
allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including
Mycoplasma and
legionellosis. It was first marketed by
Eli Lilly and Company, and it is today commonly known as EES (erythromycin ethylsuccinate, an ester
prodrug that is commonly administered). It is also occasionally used as a prokinetic agent.
In structure, this macrocyclic compound contains a 14-membered
lactone ring with ten asymmetric centers and two sugars (
L-
cladinose and
D-
desosamine), making it a compound very difficult to produce via synthetic methods.
Erythromycin is produced from a strain of the actinomycete
Saccharopolyspora erythraea.
Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer
Eli Lilly
in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to
isolate erythromycin from the metabolic products of a strain of
Streptomyces erythreus (designation changed to "
Saccharopolyspora erythraea") found in the samples.
Lilly filed for patent protection of the compound and U.S. patent
2,653,899 was granted in 1953. The product was launched commercially in
1952 under the brand name
Ilosone (after the
Philippine region of
Iloilo where it was originally collected). Erythromycin was formerly also called
Ilotycin.
In 1981, Nobel laureate (1965 in chemistry) and professor of chemistry at
Harvard University (
Cambridge, MA)
Robert B. Woodward (posthumously), along with a large number of members from his research
group, reported the first stereocontrolled asymmetric chemical synthesis
of erythromycin.
The antibiotic
clarithromycin was invented by scientists at the Japanese drug company
Taisho Pharmaceutical in the 1970s as a result of their efforts to overcome the acid instability of erythromycin.
Scientists at
Chugai Pharmaceuticals discovered an erythromycin-derived
motilin agonist called
mitemcinal that is believed to have strong
prokinetic properties (similar to erythromycin) but lacking antibiotic properties. At the present time, erythromycin is commonly used
off-label for gastric motility indications such as
gastroparesis.
If mitemcinal can be shown to be an effective a prokinetic agent, it
would represent a significant advance in the GI field as treatment with
this drug would not carry the risk of unintentional selection for
antibiotic-resistant bacteria.
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