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ANTIBIOTICS
From Bacterial and Fungal Cells to Healthcare
A Brief History of Antibiotics
•
1928 Alexander Fleming isolated
penicillin from a mould Penicillium
notatum.
•
1930 First record of penicillin being
used to cure a disease. A crude extract
was used to clear an eye infection in a
three-year old boy.
•
1939 Ernst Chain & Howard
Florey started to isolate and purify
penicillin, which was essential to help
combat infections during World War
II.
•
1944 Selman Waksman and
colleagues isolated streptomycin from
a soil bacterium Streptomyces griseus.
Streptomyces bacteria have been the
source of almost two-thirds of all
known natural antibiotics and the
majority of new antibiotics for the
past 50 years, including the
tetracyclines and erythromycin.
•
1945 Fleming, Chain & Florey
share the Nobel Prize.
•
Today, UK scientists are sequencing
the genome of Streptomyces coelicolor,
which may lead to new approaches to
the production of antibiotics.
Sequencing one species in detail will
provide valuable information that can
be applied to many other species.
What is an
antibiotic?
An antibiotic is a
substance produced by
a living thing that is
capable of destroying
or inhibiting the
growth of another
living thing. Generally
antibiotics are
produced by bacteria
or fungi, although they
can come from plants,
insects, amphibians or
even mammals.
Chemists can alter the
structure of a naturally
produced substance to
make it a more
effective antibiotic.
Antibiotics like the
cephalosporins and
the penicillins are
extremely valuable to
industry.
bbsrc
biotechnology and biological sciences
research council
How do antibiotics work?
Antibiotics may be used to treat
bacterial disease by preventing the
formation of bacterial cell walls.
Some antibiotics like penicillin and
cephalosporin inhibit the synthesis
of peptide links between
peptidoglycan molecules in bacterial
cell walls. This causes the cell wall to
become weak and the bacterium to
explode.These peptidoglycans are not
found in mammalian cells, which is why
the antibiotics are selectively toxic towards
bacteria.
Some antibiotics interfere with DNA replication. Rifampicin binds to
RNA polymerase in bacteria and prevents transcription.The anthracyclines
interfere with DNA synthesis in all organisms, but the effect is most marked
in rapidly growing cancer cells.
Some antibiotics interfere with protein synthesis. Antibiotics like
streptomycin and tetracycline interfere with protein synthesis often by
binding to the ribosomes. Some antibiotics can only bind to ribosomes
from bacteria, but some like tetracycline can bind to ribosomes in mammals
and bacteria. They are not harmful to humans because they are excluded
from mammalian cells. Some antibiotics also promote the synthesis of
abnormal proteins.
Some antibiotics prevent cell membrane function. Most of the new
peptide antibiotics work by binding to molecules (usually sterols) in the cell
wall. This distorts the lipid bilayer and opens channels in the membrane
that causes the cell contents to leak out.
Bacteriostatic antibiotics prevent growth and multiplication, which gives
the body’s immune system a better chance of fighting a bacterial infection.
Bactericidal antibiotics kill their target bacteria.
Bacterial resistance
Bacterial infection is a serious health problem. So called “superbugs” are
antibiotic-tolerant bacteria that cause health problems, especially in
Intensive Care Units where the most vulnerable are treated. In some
countries superbugs are endemic and some diseases are re-emerging as a
threat in the UK. Superbugs can evolve resistance either by altering the
target, by defusing the antibiotic or by preventing its uptake. Bacteria can
become resistant by mutations in their own genes or by receiving genetic
information from elsewhere.
How can the scientists overcome resistance to antibiotics?
• One way of tackling the problem of bacteria becoming resistant to
antibiotics is to redesign the antibiotics. However the bacteria can also
redesign their resistance.
• Another approach is to create new antibiotics by mixing and matching
the ingredients of existing ones.
• Research at the University of Cambridge is looking at the pathway of
enzymes that make chemicals, that include the antibiotic erythromycin.
Changing this pathway may produce new antibiotics.
• Research at the Institute for Animal Health has shown that
bacteriophages (viruses that attack and destroy bacteria) can control
bacterial infections in different tissues in animals.This suggests that
bacteriophage treatment could be effective in treating and possibly
preventing bacterial diseases in humans.
• Many drugs work by binding to a specific site
on a protein and altering its function. By
using computer modelling, scientists can
model this binding site and design drugs
to fit it more snugly so that they are
more effective.
The tuberculosis story
Historically, many people have been victims of turberculosis including
Jane Austen and Henry VIII, this disease is still a problem today. Multi-drug
resistant tuberculosis is found in many parts of the world and is now a
concern in the UK. By 1995, one in seven cases of tuberculosis was resistant
to all known antibiotics. In 2001, young people in London were warned
about the risks of catching tuberculosis in clubs and bars.
Scientists such as Dr Jim Naismith
from the University of St Andrews are
looking at new targets for treatment
of tuberculosis. He is trying to find a
new class of antibiotics by studying
the structure of enzymes in the
bacteria that might be targets.
The structure of an enzyme found in
Some antibiotics can only work when
Mycobacterium tuberculosis
bacteria are in their growing state.
Scientists have discovered a natural chemical that can change the bacteria
from their dormant state to their growing state making them more
susceptible to antibiotics, which may have implications for treating
tuberculosis.
How can we help prevent resistance
1. Patients should take the full course of antibiotics to kill ALL of the
bacteria. In reality patients stop taking their medication when they feel
better, allowing some partially-resistant bacteria to survive and spread.
2. By regulating the use of antibiotics in animal feeds and medicine. In
Europe the antibiotics that are used for animal feeds are not used in
medicines for humans.
3. By selling antibiotics only with a prescription, which will ensure that a
full course of antibiotics is given to the patient and by advising on the
proper usage at the pharmacy and health centre.
For more information visit our exhibitions website at
www.bbsrc.ac.uk/life