Antimicrobials
👉Chlorine containing antibiotic, chloramphenicol,
produced by microorganisms is very effective for the
treatment of typhoid fever.
👉Synthetic halogen
compounds, viz. chloroquine is used for the treatment
of malaria
👉Halothane is used as an anaesthetic
during surgery.
👉Certain fully fluorinated compounds
are being considered as potential blood substitutes
in surgery.
👉An antimicrobial tends to destroy/prevent development or inhibit the
pathogenic action of microbes such as bacteria (antibacterial drugs),
fungi (antifungal agents), virus (antiviral agents), or other parasites
(antiparasitic drugs) selectively. Antibiotics, antiseptics and disinfectants
are antimicrobial drugs.
👉An antibiotic now refers to a substance produced wholly or
partly by chemical synthesis, which in low concentrations inhibits the
growth or destroys microorganisms by intervening in their metabolic
processes.
👉Paul Ehrlich investigated arsenic
based structures in order to produce less toxic substances for the
treatment of syphilis. He developed the medicine, arsphenamine,
known as salvarsan. Paul Ehrlich got Nobel prize for Medicine in
1908 for this discovery. It was the first effective treatment discovered
for syphilis. Although salvarsan is toxic to human beings, its effect on
the bacteria, spirochete, which causes syphilis is much greater than
on human beings.
👉At the same time, Ehrlich was working on azodyes
also. He noted that there is similarity in structures of salvarsan and
azodyes. The –As = As– linkage present in arsphenamine resembles
the –N = N – linkage present in azodyes in the sense that arsenic atom
is present in place of nitrogen. He also noted tissues getting coloured
by dyes selectively. Therefore, Ehrlich began to search for the
compounds which resemble in structure to azodyes and selectively
bind to bacteria. In 1932, he succeeded in preparing the first effective
antibacterial agent, prontosil, which resembles in structure to the
compound, salvarsan. Soon it was discovered that in the body prontosil
is converted to a compound called sulphanilamide, which is the real
active compound. Thus the sulpha drugs were discovered. A large
range of sulphonamide analogues was synthesised. One of the most
effective is sulphapyridine.
👉
👉Alexander Fleming
in 1929, of the antibacterial properties of a Penicillium fungus.
👉Antibiotics have either cidal (killing) effect or a static (inhibitory) effect
on microbes. A few examples of the two types of antibiotics are as follows:
Bactericidal:
Penicillin
Aminoglycosides
Ofloxacin
Bacteriostatic:
Erythromycin
Tetracycline
Chloramphenicol
👉The range of bacteria or other microorganisms that are affected by a
certain antibiotic is expressed as its spectrum of action.
👉Antibiotics which
kill or inhibit a wide range of Gram-positive and Gram-negative bacteria
are said to be broad spectrum antibiotics.
👉Those effective mainly against
Gram-positive or Gram-negative bacteria are narrow spectrum
antibiotics.
👉If effective against a single organism or disease, they are
referred to as limited spectrum antibiotics.
👉Penicillin G has a narrow
spectrum.
👉Ampicillin and Amoxycillin are synthetic modifications of
penicillins. These have broad spectrum.
👉It is absolutely essential to test
the patients for sensitivity (allergy) to penicillin before it is administered.
👉Chloramphenicol, isolated in 1947, is a broad spectrum antibiotic.
It is rapidly absorbed from the gastrointestinal tract and hence can
be given orally in case of typhoid, dysentery, acute fever, certain
form of urinary infections, meningitis and pneumonia.
👉Vancomycin
and ofloxacin are the other important broad spectrum antibiotics.
👉The antibiotic dysidazirine is supposed to be toxic towards certain
strains of cancer cells.
👉
👉Antiseptics are applied to the living tissues such as wounds, cuts,
ulcers and diseased skin surfaces. Examples are furacine,
soframicine, etc. These are not ingested like antibiotics.
👉Commonly
used antiseptic, dettol is a mixture of chloroxylenol and terpineol.
👉Bithionol (the compound is also called bithional) is added to soaps to
impart antiseptic properties.
👉Iodine is a powerful antiseptic. Its
2-3 per cent solution in alcohol water
mixture is known as
tincture of iodine. It is applied
on wounds.
👉Iodoform is also used
as an antiseptic for wounds
👉Boric
acid in dilute aqueous solution is
weak antiseptic for eyes.
👉Disinfectants are applied to inanimate objects such as floors,
drainage system, instruments, etc.
👉Same substances can act as an
antiseptic as well as disinfectant by varying the concentration. For
example, 0.2 per cent solution of phenol is an antiseptic while its one
percent solution is disinfectant.
👉Chlorine in the concentration of 0.2 to 0.4 ppm in aqueous solution
and sulphur dioxide in very low concentrations, are disinfectants.
👉
👉Birth control pills essentially contain a
mixture of synthetic estrogen and progesterone derivatives.
👉It is known that progesterone suppresses
ovulation. Synthetic progesterone derivatives are more potent than
progesterone. Norethindrone is an
example of synthetic progesterone
derivative most widely used as
antifertility drug.
👉The estrogen
derivative which is used in combination
with progesterone derivative is
ethynylestradiol (novestrol).
👉
👉Intext Questions
16.1 Sleeping pills are recommended by doctors to the patients suffering from
sleeplessness but it is not advisable to take its doses without consultation
with the doctor. Why ?
16.2 With reference to which classification has the statement, “ranitidine is an
antacid” been given?
👉Drug chemistry
centres around arresting microbes/destroying microbes, preventing the body
from various infectious diseases, releasing mental stress, etc. Thus, drugs like
analgesics, antibiotics, antiseptics, disinfectants, antacids and tranquilizers are
used for specific purpose.
👉What is meant by the term ‘broad spectrum antibiotics’ ? Explain.
👉In addition to the genomic DNA (the
single chromosome/circular DNA), many
bacteria have small circular DNA outside the
genomic DNA. These smaller DNA are called
plasmids. The plasmid DNA confers certain
unique phenotypic characters to such bacteria.
One such character is resistance to antibiotics.
👉when one analyses plant, fungal and microbial cells,
one would see thousands of compounds other than these called primary
metabolites, e.g. alkaloids, flavonoids, rubber, essential oils, antibiotics,
coloured pigments, scents, gums, spices. These
are called secondary metabolites
👉
👉Excess use of herbicides, pesticides, etc., has only resulted in
selection of resistant varieties in a much lesser time scale. This is also true for
microbes against which we employ antibiotics or drugs against eukaryotic
organisms/cell. Hence, resistant organisms/cells are appearing in a time
scale of months or years and not centuries. These are examples of evolution
by anthropogenic action.
👉Explain antibiotic resistance observed in bacteria in light of Darwinian
selection theory.
👉The discovery of antibiotics, and synthetic plant-derived drugs,
anaesthetics have changed medical practice on one hand
and human health on the other hand.
👉Discovery of antibiotics and various other drugs has also
enabled us to effectively treat infectious diseases.
👉Even in industry, microbes are used to synthesise a number of products
valuable to human beings. Beverages and antibiotics are some examples.
👉Anti is
a Greek word that means ‘against’, and bio means
‘life’, together they mean ‘against life’ (in the
context of disease causing organisms); whereas with reference to human
beings, they are ‘pro life’ and not against.
👉Antibiotics are chemical
substances, which are produced by some microbes and can kill or retard
the growth of other (disease-causing) microbes.
👉Do you
know that Penicillin was the first antibiotic to be discovered, and it was a
chance discovery? Alexander Fleming while working on Staphylococci
bacteria, once observed a mould growing in one of his unwashed culture
plates around which Staphylococci could not grow. He found out that it
was due to a chemical produced by the mould and he named it Penicillin
after the mould Penicillium notatum.
However, its full potential as an
effective antibiotic was established much later by Ernest Chain and
Howard Florey. This antibiotic was extensively used to treat American
soldiers wounded in World War II. Fleming, Chain and Florey were awarded
the Nobel Prize in 1945, for this discovery.
👉After Penicillin, other antibiotics were also purified from other
microbes. Can you name some other antibiotics and find out their
sources?
👉Antibiotics have greatly improved our capacity to treat deadly
diseases such as plague, whooping cough (kali khansi ), diphtheria (gal
ghotu) and leprosy (kusht rog)
👉Antibiotics like penicillins produced by useful microbes are used to kill
disease-causing harmful microbes.
👉 Antibiotics have played a major role
in controlling infectious diseases like diphtheria, whooping cough and
pneumonia.
👉Name any two species of fungus, which are used in the production of
the antibiotics.
👉Bioprocess engineering: Maintenance of sterile (microbial
contamination-free) ambience in chemical engineering processes
to enable growth of only the desired microbe/eukaryotic cell in
large quantities for the manufacture of biotechnological products
like antibiotics, vaccines, enzymes, etc.
👉The construction of the first recombinant
DNA emerged from the possibility of linking a gene encoding antibiotic
resistance with a native plasmid (autonomously replicating circular
extra-chromosomal DNA) of Salmonella typhimurium.
👉Stanley Cohen and
Herbert Boyer accomplished this in 1972 by isolating the antibiotic
resistance gene by cutting out a piece of DNA from a plasmid which was
responsible for conferring antibiotic resistance.
👉The linking of antibiotic resistance gene
with the plasmid vector became possible with the enzyme DNA ligase,
👉This makes a new
combination of circular autonomously replicating DNA created in vitro
and is known as recombinant DNA. When this DNA is transferred into
Escherichia coli, a bacterium closely related to Salmonella, it could
replicate using the new host’s DNA polymerase enzyme and make multiple
copies. The ability to multiply copies of antibiotic resistance gene in
E. coli was called cloning of antibiotic resistance gene in E. coli.
👉Transformation is a procedure through which a
piece of DNA is introduced in a host bacterium . Normally, the genes encoding
resistance to antibiotics such as ampicillin, chloramphenicol,
tetracycline or kanamycin, etc., are considered useful selectable
markers for E. coli. The normal E. coli cells do not carry resistance
against any of these antibiotics.
👉The
ligation of alien DNA is carried out at
a restriction site present in one of the
two antibiotic resistance genes. For
example, you can ligate a foreign DNA
at the BamH I site of tetracycline
resistance gene in the vector pBR322.
The recombinant plasmids will lose
tetracycline resistance due to insertion
of foreign DNA but can still be selected
out from non-recombinant ones by
plating the transformants on
tetracycline containing medium.
👉Non- recombinants will grow on the medium containing both the
antibiotics.
👉one antibiotic resistance gene helps in
selecting the transformants, whereas the other antibiotic resistance gene gets ‘inactivated due to insertion’ of alien DNA, and helps in
selection of recombinants.
👉Selection of recombinants due to inactivation of antibiotics is a
cumbersome procedure because it requires simultaneous plating
on two plates having different antibiotics. Therefore, alternative
selectable markers have been developed which differentiate
recombinants from non-recombinants on the basis of their ability
to produce colour in the presence of a chromogenic substrate.
👉Insertion of Recombinant DNA into the Host
Cell/Organism:
There are several methods of introducing the ligated DNA into recipient
cells. Recipient cells after making them ‘competent’ to receive, take up
DNA present in its surrounding. So, if a recombinant DNA bearing gene
for resistance to an antibiotic (e.g., ampicillin) is transferred into E. coli
cells, the host cells become transformed into ampicillin-resistant cells. If
we spread the transformed cells on agar plates containing ampicillin, only
transformants will grow, untransformed recipient cells will die. Since, due
to ampicillin resistance gene, one is able to select a transformed cell in the
presence of ampicillin. The ampicillin resistance gene in this case is called
a selectable marker.
👉Heterotrophic bacteria are most abundant in
nature. The majority are important decomposers.
Many of them have a significant impact on human
affairs. They are helpful in making curd from milk,
production of antibiotics, fixing nitrogen in legume etc.
👉fungi cause diseases in plants and animals; wheat
rust-causing Puccinia is an important example. Some are the source of
antibiotics, e.g., Penicillium.
