Bacterial resistance to antibiotics
Bacterial Resistance to Antibiotics (page 3)
Bacterial mechanisms of antibiotic resistance
Several mechanisms have evolved in bacteria which confer them with antibioticresistance. These mechanisms can either chemically modify the antibiotic, render itinactive through physical removal from the cell, or modify target site so that it is notrecognized by the antibiotic.
The most common mode is enzymatic inactivation of the antibiotic. An existingcellular enzyme is modified to react with the antibiotic in such a way that it nolonger affects the microorganism. An alternative strategy utilized by many bacteriais the alteration of the antibiotic target site. These and other mechanisms are shownin the the figure and accompanying table below.
Three mechanisms of antibiotic resistance in bacteria. Most, but not all,
resistance mechanisms are encoded by plasmids, which are potentially
transmissible to other bacteria. Clockwise. 12 o'clock: Efflux pumps are
high-affinity reverse transport systems located in the membrane that
transport the antibiotic out of the cell. This is the mechanism of resistance
to tetracycline. 4 o'clock: A specific enzyme modifies the antibiotic in a way
that it loses its activity. In the case of streptomycin, the antibiotic is
chemically modified so that it will no longer bind to the ribosome to block
protein synthesis. 9 o'clock: An enzyme is produced that degrades the
antibiotic, thereby inactivating it. For example, the penicillinases are a
group of beta-lactamase enzymes that cleave the beta lactam ring of the
Method of resistance
β-lactams, Erythromycin, eliminates or reduces binding ofLincomycin
The acquisition and spread of antibiotic resistance in bacteria
The development of resistance is inevitable following the introduction of a newantibiotic. Initial rates of resistance to new drugs are normally on the order of 1%.
However, modern uses of antibiotics have caused a huge increase in the number ofresistant bacteria. In fact, within 8-12 years after wide-spread use, strains resistantto multiple drugs become widespread. Multiple drug resistant strains of somebacteria have reached the proportion that virtually no antibiotics are available fortreatment.
Antibiotic resistance in bacteria may be an inherent trait of the organism (e.g. a
particular type of cell wall structure) that renders it naturally resistant
, or it may
by means of mutation in its own DNA or acquisition of resistance-
conferring DNA from another source.
Inherent (natural) resistance
. Bacteria may be inherently resistant to an
antibiotic. For example, an organism lacks a transport system for an antibiotic; or
an organism lacks the target of the antibiotic molecule; or, as in the case of Gram-
negative bacteria, the cell wall is covered with an outer membrane that establishes a
permeability barrier against the antibiotic.
. Several mechanisms are developed by bacteria in order to
acquire resistance to antibiotics. All require either the modification of existing
genetic material or the acquisition of new genetic material from another source.
Vertical gene transfer
The spontaneous mutation frequency for antibiotic resistance is on the order of
about of about 10-8- 10-9. This means that one in every every 108- 109 bacteria in
an infection will develop resistance through the process of mutation. In E. coli
, it has
been estimated that streptomycin resistance is acquired at a rate of approximately
10-9 when exposed to high concentrations of streptomycin. Although mutation is a
very rare event, the very fast growth rate of bacteria and the absolute number of
cells attained means that it doesn't take long before resistance is developed in a
Once the resistance genes have developed, they are transferred directly to all the
bacteria's progeny during DNA replication. This is known as vertical gene transfer
or vertical evolution
. The process is strictly a matter of Darwinian evolution driven
by principles of natural selection: a spontaneous mutation in the bacterial
chromosome imparts resistance to a member of the bacterial population. In the
selective environment of the antibiotic, the wild type (non mutants) are killed and
the resistant mutant is allowed to grow and flourish
Horizontal gene transfer
Another mechanism beyond spontaneous mutation is responsible for the acquisition
of antibiotic resistance. Lateral or horizontal gene transfer
(HGT) is a process
whereby genetic material contained in small packets of DNA can be transferred
between individual bacteria of the same species or even between different species.
There are at least three possible mechanisms of HGT, equivalent to the threeprocesses of genetic exchange in bacteria. These are transduction, transformation orconjugation.
Conjugation occurs when there is direct cell-cell contact between two bacteria(which need not be closely related) and transfer of small pieces of DNA calledplasmids takes place. This is thought to be the main mechanism of HGT.
Transformation is a process where parts of DNA are taken up by the bacteria fromthe external environment. This DNA is normally present in the external environmentdue to the death and lysis of another bacterium.
Transduction occurs when bacteria-specific viruses (bacteriophages) transfer DNAbetween two closely related bacteria.
Mechanisms of horizontal gene transfer (HGT) in bacteria
The combined effects of fast growth rates to large densities of cells, geneticprocesses of mutation and selection, and the ability to exchange genes, account forthe extraordinary rates of adaptation and evolution that can be observed in thebacteria. For these reasons bacterial adaptation (resistance) to the antibioticenvironment seems to take place very rapidly in evolutionary time. Bacteria evolvefast!
Tests for sensitivity and resistance to antibiotics. (Left) The size of the zones of
inhibition of microbial growth surrounding the antibiotic disks on the plate are an
indication of microbial susceptibility to the antibiotic. (Right) By the use of these
disks it is also possible to detect the occurrence of individual mutants within the
culture that have developed antibiotic resistance. This image shows a close-up of
the novobiocin disk (marked by an arrow on the whole plate) near which individual
mutant cells in the bacterial population that were resistant to the antibiotic and
have given rise to small colonies within the zone of inhibition.
Kenneth Todar, Ph.D. All rights reserved. - www.textbookofbacteriology.net
X-ray structures of Thermoactinomyces vulgaris R-47 α -Amylase 2 with Acarbose and β -Cyclodextrin Shigehiro KAMITORI*1, Akashi OHTAKI1, Masahiro MIZUNO2, Takashi TONOZUKA2 1Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan 2Department of Applied Biological Science, Tokyo University of A
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