Basis of Resistance
Resistance by bacteria against antibiotic may be classified as:
a)
Nongenetic basis
b)
Genetic basis
Nongenetic basis of resistance plays a less important role in the
development of drug resistance:
a)
Certain bacteria under ordinary circumstances are usually killed by
penicillins. But these bacteria, if lose their cell wall and become protoplast,
become nonsusceptible to the action of cell wall–acting drug such as
penicillins.
b)
In certain conditions, such as in the abscess
cavity, bacteria can be walled off, which prevents drugs to penetrate effec-tively
into bacteria. Surgical drainage of pus, however, makes these bacteria again
susceptible to the action of antibiotics.
c)
Presence of foreign bodies (such as surgical
implants and cath-eters) and penetration injury caused by splinters and
sharpen-ers make successful antibiotic treatment more difficult.
d)
Nonreplicating bacteria in their resting stage are less sensi-tive
to the action of cell wall inhibitors such as penicillin and cephalosporins.
This is particularly true for certain bacteria such as Mycobacterium tuberculosis that remains in resting stage in tissues
for many years, during which it is insensitive to drugs. However, when these
bacteria begin to multiply, they become susceptible to antibiotics.
The genetic basis of drug resistance, mediated by genetic change in
bacteria, is most important in the development of drug resistance in bacteria.
This is of three types as follows: (a)
chromosome-mediated resistance, (b)
plasmid-mediated resistance, and (c)
transposons-mediated resistance.
Chromosome-mediated resistance occurs as a result of spon-taneous
mutation. This is caused by mutation in the gene that codes for either the
target of drug or the transport system in the membrane of the cell wall, which
controls the entry of drugs into cells. The frequency of chromosomal mutation
is much less than the plasmid-mediated resistance. It varies between 10 7
and 10 9.
Plasmid-mediated drug resistance in bacteria occurs by transfer of
plasmid and genetic materials. It is mediated by resistance plasmid, otherwise
known as R factor.
R factors: These are circular,
double-stranded DNA moleculesthat carry the genes responsible for resistance
against variety of antibiotics. These factors may carry one or even two or more
resistant genes. The genes encode for a variety of enzymes that destroy the
antibiotics by degrading antibiotics or modify membrane transport system. For
example, the genes code for enzymes like -lactamases that destroy -lactam ring
(which is responsible for the antibactericidal action of -lactam antibiot-ics,
such as penicillins and cephalosporins). Table 9-3 lists dif-ferent mechanisms
of plasmid-mediated resistance in bacteria.
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Transposons-mediated drug resistance
Drug resistance is also mediated by transposons that often carry
the drug resistance genes. Transposons are small pieces of DNA
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