Denna sida på svenska. Antibiotics is the name of a group of medicines that combats bacteria in living organisms. Many people think that antibiotics and penicillin are exactly the same thing - others believe instead that antibiotics is a form of penicillin. As we shall see the truth is that penicillin is a form of antibiotics, a fact which sometimes can be of use to be aquainted with.
Penicillin was one of the first forms of antibiotics that could be massproduced, and this might as well be the main reason why these names so easily gets mixed up. But soon the methods of massproducing other kinds of antibiotics, such as streptomycin, tetracycline and chloramphenicol was developed. In the beginning these substances was grown and filtered, but today they are developed synthetically.
An ideal antibiotic is poisonous to the bacteria that it has to combat and harmless to the living organism that it has to cure. Often the case instead is that the poisonousness is relative - in a certain concentration it is harmless to the host and lethal to the bacteria. This selectiveness can be caused by the fact that a special receptor is needed for the medicine to work, or that the medicine stops a biochemical event that is essential for the bacteria but not for the host.
Antibiotics are roughly divided into four groups
depending on their actual way of action, and these four
groups are:
A The ones inhibiting the cell wall synthesis.
B The ones inhibiting the cell membrane function.
C The ones inhibiting the protein synthesis.
D The ones inhibiting the nucleic acid synthesis.
Group A (that inhibits the cell wall synthesis) contains substances such as penicillins, bacitracin, cephalosporins, cycloserine and vancomycin and so on. Bacteria has a rigid cell wall that gives the bacteria its typical shape. Injury to the cell wall easily causes the bacteria to explode. In the cell wall there are some chemically distinct receptors that consists of short peptide chains. If penicillin attach itself to one of these receptors the bacteria will explode. It is not exactly known today how this works except that the synthesis in the cell wall is involved, but it is known that the receptors can be changed geneticly.
Group B (that inhibits the cell membrane function) contains substances such as amphotericin B, colistin, imidazoles, polyenes and polymyxins and so on. These substances have a slightly different mode of action than the substances of group A. All living cells have a cytoplasmic membrane that surrounds the cytoplasm inside the cell, and this membrane acts as a permeability barrier, transports things in and out of the cell. Thus this membrane controls the internal composition of the cell. If the functions of this membrane gets disrupted ions and makromolecules will travel out of the cell which leads to cell damage or death of the cell. Fungi and bacteria have different cell membranes than mammals and therefore it is possible to attach to their cell membranes in a chemical level. This way the polyenes attack the cell membranes of fungi and the polymyxines attacks the cell membranes of bacteria.
Group C (that inhibits the protein synthesis) contains substances such as chloramphenicol, erythromycins, lincomycins, tetracyclines and aminoglycosides and so on. This is the most interesting group concerning small mammals. Exactly how these substances works is not yet known. But it is pretty well established that the ribosomes are involved, and it is known that bacteria and mammals have totally different ribosomes. The protein synthese (the translation and transcription of genetic material) means that the ribosomes build together amino acids following special patterns (mRNA) to long peptide chains. Completed, these peptide chains are called proteins.
1 Aminoglycosides consists of streptomycin, kanamycin, neomycin, tobramycin and amikain, and so far as we know these all have approximately the same kind of functions. Streptomycin is the most studied substance among the aminoglycosides. In a way you can say that it attaches itself to a specific place at the ribosome and that way disrupts the reading of mRNA, causing the wrong amino acid to be attached into the peptide chain and the result will be a protein that is nonfunctional. But this is not the whole truth since the ribosomes cooperates in constructing proteins and this cooperation is disrupted by the streptomycin, and it also disrupts the normal activities of initiating the building of a peptide chain. All of this happens more or less simultaneously and commonly leads to the death of the bacteria. There are three different known ways that the bacteria can become resistent towards the aminoglycosides, the bacteria can deny its entrance into the bacteria, the specific receptor on the ribosome can be missing and the bacteria can produce different kinds of enzymes that can destroy the antibiotic.
2 Tetracyclines inhibits the building of proteins by blocking new amino acids from being attached to the peptide chain by blocking out certain ions. This action stops when you stop giving the medicine. The bacteria normally concentrates the medicine inside itself and can become resistent by stopping this action. Mammals never concentrates the medicine in their cells.
3 Chloramphenicol gives the same result as the tetracyclins but use another mode of action, it inhibits the construction of a substance that is necessary in the protein synthesis. The effect goes away when you stop giving the medication. The bacteria can become resistent by producing an enzyme that destroys the medicine.
4 Macrolides contain erythromycins and oleandomycins. Their mode of action is not exactly known but it is believed that they either interrupts the construction of peptide chains or that they interrupts the starting procedures of this construction. Some bacteria are resistent by the fact that they do not have receptors for the macrolides to attach to.
5 Lincomycins consists of lincomycin and clindamycin, these have principally the same kind of action as the macrolides.
Group D (that inhibits the nucleic
acid synthesis) contains substances such as quinolones,
pyrimethamine, rifampin, sulfonamides and trimethoprim
and so on and these have a different way of action
compared to the other groups.
Rifampin binds
itself to a substance called RNA-polymeras inside
the bacteria and by doing so it inhibits the RNA
synthese (RNA is a nucleic acid). The bacteria can
become resistent if there is a change in the
RNA-polymeras so that the rifampin cannot bind itself
to it. Rifampin also have a inhibiting effect against
the poxviruses in a late stage of construction.
All quinolones and fluoroquinolones stops the DNA
synthese by blocking the DNA gyras.
A very important substance is p-aminobenzoic acid,
also called PABA. PABA is deeply involved in the
folic acid synthesis, and folic acid is a part of
the nucleic acid synthesis. (Folic acid is a substance
that is commonly found in vitaminpills.)
Sulfonamides are structural analogues of PABA and
can therefore take the place of PABA in the folic
acid synthesis - except that you get a structural
analogue of folic acid which cannot take the place
of the real folic acid and therefore have no function
in the cell and the nucleic acid synthesis stops when
there is no real folic acid left. Mammals cannot
produce folic acid and are therefore not affected
at all by sulfonamides, but many bacteria produce
folic acid and are therefore sensitive to this
medication. Unfortunately some bacteria produce
much more PABA than they use up which means that
they are less sensitive to sulfonamides.
Trimethoprim chemically reduces a stage in the
sequence leading to the synthesis of DNA, 50.000
times more efficiently in bacteria than in mammalian
cells.
In combining trimethoprim and sulfonamides in the
same medicine these substances show a synergic effect,
they are a lot more effective together than the
summarized effect of the different medicines. The
usual combination is five parts sulfonamide to one
part trimethoprim. (Borgal and Baktrim are good
examples, and often used with small mammals.)
There is another substance, pyrimethamine, that
have almost the same mode of action as trimethoprim
except that it is more poisonous to mammals.
Pyrimethamine can be combined with sulfonamides in
the same way as trimethoprim, and this combination
is used as a treatment for some graver deceases
such as malaria.
Several substances that inhibits the nucleid acid
synthesis are selective enough to be used as
antivirus medicines.
REFERENCE: Medical Microbiology - Brooks, Melnick & Adelberg.
Written by: Eva Johansson.
Copyright Eva Johansson.
Last update: 11th of August 2006.