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ANTIBIOTICS

An antibiotic is a drug that kills or stops the growth of bacteria, without harming the cells of the
infected organism.

Antibiotics are derived from living organisms, although they are often made more effective by
various chemical processes.

There are a wide range of antibiotics to treat bacterial infections. Other antimicrobial drugs such
as isoniazid, used for the treatment of TB, are synthetic (made in laboratories).

How antibiotics work


Antibiotics interfere with some aspect of growth or metabolism of the target bacterium. These
include:

 synthesis of bacterial cell walls


 activity of proteins in the cell surface membrane
 enzyme action
 DNA synthesis and replication
 protein synthesis

Bacterial cells have walls made of peptidoglycans. These are long molecules containing
peptides
(Chains of amino acids) and sugars. In the bacterial cell wall, peptidoglycans are held together
by cross-links that form between them.
Penicillin prevents the synthesis of the cross-links between the peptidoglycan polymers in the
cell walls of bacteria by inhibiting the enzymes that build these cross-links. This means that
penicillin is only active against bacteria while they are growing.

When a newly formed bacterial cell is growing, it secretes enzymes called autolysins, which
make little holes in its cell wall. These little holes allow the wall to stretch so that new
peptidoglycan chains can link together. Penicillin prevents the peptidoglycan chains from linking
up, but the autolysins keep making new holes. The cell wall therefore becomes progressively
weaker. Bacteria live in watery environments and take up water by osmosis. When they are
weakened, the cell walls cannot withstand the pressure potential exerted on them by the cell
contents and the cells burst.
This explains why penicillin does not affect human cells. Our cells do not have walls. This also
explains why penicillin and other antibiotics do not affect viruses, which do not even have cells,
let alone cell walls. Viruses do not have the targets shown in For example, when a virus
replicates, it uses the host cell’s mechanisms for transcription and translation and antibiotics do
not bind to the proteins that host cells use in these processes.
Eukaryotic cells have proteins that are different from those in bacteria so they are unaffected by
such antibiotics. Other drugs, called antivirals, are used to control viral infections.

There are fewer antivirals than there are antibiotics. Penicillin first became available for treating
disease in the 1940s. It was hailed as a wonder drug that could be used to wipe out all the
diseases caused by bacteria.

To begin with, this seemed to be true, but very quickly it became clear that this was not going to
happen even though other antibiotics, such as streptomycin, soon became available.

Some types of bacteria are not sensitive to particular antibiotics: for example, penicillin is not
effective against M. tuberculosis. Even among the types of bacteria that were killed by penicillin,
there were certain strains that were not affected. These strains had become resistant to antibiotics.
During the 70 years since the introduction of antibiotics, most pathogenic bacteria have become
resistant to one or more types of antibiotic.
Antibiotic resistance
 Penicillin has no effect on M. tuberculosis because

 the thick cell wall of this bacterium is not very permeable

 the bacterium has a gene that codes for an enzyme that catalyses the breakdown of penicillin.

 Proteins in the membranes of other species of bacteria can inactivate antibiotics so they have no effect;

 bacterial membranes also have proteins that pump out antibiotics if they enter the cytoplasm. In
some cases, the antibiotic simply cannot bind to the intended site of action.

Bacteria that are sensitive to an antibiotic are described as being susceptible to that antibiotic. They may
become resistant if they gain a gene coding for a protein that
protects them from the antibiotic.

Soil bacteria have many resistance mechanisms as they grow in an environment where there are many
molecules that interfere with their metabolism. These resistance mechanisms are very similar to those found
in pathogenic bacteria.

Before the introduction of antibiotics, enzymes known as beta-lactamases were not common among
pathogenic bacteria. The genes for these enzymes have spread into many different forms of bacteria and it is
believed that they have come from soil bacteria.

Penicillin has a structure that can be broken down by β-lactamase (penicillinase) enzymes. Pathogenic
bacteria that have become resistant to penicillin have often done so because they have acquired the genes that
code for these enzymes.

Antibiotic resistance can arise when an existing gene within the bacterial genome changes spontaneously to
give rise to a nucleotide sequence that codes for a slightly
different protein that is not affected by the antibiotic.

This change in DNA is a mutation. When someone takes penicillin to treat a bacterial infection, bacteria that
are susceptible to penicillin will die. In most cases, if the dose is followed correctly, this will be the entire
population of the disease-causing bacteria. However, if the dose is not followed, perhaps because people stop
taking the penicillin when they feel better as the symptoms disappear, then some susceptible bacteria survive
and if any mutations occur these might confer resistance. The next time there is an infection with this strain of
bacteria, penicillin may not be effective.

Bacteria have only one copy of each gene, since they only have a single loop of double-stranded DNA. This
means that a mutant gene will have an immediate effect on any bacterium possessing it. These individuals have
a tremendous advantage. Bacteria without this mutant gene will be killed, while those bacteria resistant to
penicillin survive and reproduce. Bacteria reproduce asexually by binary fission; the DNA in the bacterial
chromosome is replicated and the cell divides into two, with each daughter cell receiving a copy of the
chromosome. This happens very rapidly in ideal conditions, and even if there was initially only one resistant
bacterium, it might produce ten thousand million descendants within 24 hours. A large population of a
penicillin-resistant strain of a bacterium would result. This method of spreading antibiotic resistance in a
population of bacteria is called vertical transmission.

Genes for antibiotic resistance often occur on plasmids, which are small loops of double-stranded DNA.
Plasmids are quite frequently transferred from one bacterium to another, even between different species. This
happens during conjugation when a tube forms between two bacteria to allow the movement of DNA. During
conjugation, plasmids are transferred from a donor bacterium to a recipient. Transfer of part of the DNA from
the bacterial chromosome also occurs in the same way. This method of transmission is horizontal
Transmission. Thus it is possible for resistance to a particular antibiotic to arise in one species of bacterium and
be passed on to another.
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dangerous infections after surgery, which were mostly controlled by vancomycin – an
antibiotic often used as a last resort for treating infections when everything else has
failed, so as to lessen the chances of the development of more such resistant
organisms. Then, another bacterium common in hospitals, Enterococcus faecalis,
developed resistance.

Some of the ways in which we can do to reduce bacterial resisitance this


include:
■■ using antibiotics only when appropriate and necessary;not prescribing them for viral
infections
■■ reducing the number of countries in which antibiotics are sold without a doctor’s
prescription
■■ avoiding the use of so-called wide-spectrum antibiotics and using instead an
antibiotic specific to the infection(known as narrow spectrum)
■■ making sure that patients complete their course of medication
■■ making sure that patients do not keep unused antibiotics for self-medication in the
future
■■ changing the type of antibiotics prescribed for certain diseases so that the same
antibiotic is not always prescribed for the same disease
■■ avoiding using antibiotics in farming to prevent, rather than cure, infections.

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