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Chapter 5 : Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents

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Abstract:

Over the past 63 years (1940 to 2003), the emergence and spread of bacterial resistance to the action of antibiotics and synthetic antibacterial agents are certainly the most striking examples of evolution that have arisen in bacteria. Bacterial resistance is described in terms of either phenotypic (e.g., growth patterns) or genotypic (e.g., presence or expression of genes) characteristics of bacteria, or both, and can be categorized according to origin (intrinsic versus acquired resistance) or type (single or multiple). Conjugative transposons of gram-positive as well as gram-negative bacteria represent another efficient mode of transfer of antibacterial resistance genes between phylogenetically distant bacteria genera. Horizontal gene transfer among bacteria is a perpetual phenomenon that has a significant impact on bacterial evolution. This chapter presents a general overview of the major mechanisms of bacterial resistance. Impermeability was considered to be the main mechanism of tetracycline resistance in gram-negative bacteria, due to less drug accumulation in resistant cells. The β-lactamase genes are located in the chromosome, in plasmids, or in transposons. The major mechanism of inactivation of aminoglycoside antibiotics involves aminoglycoside-modifying enzymes. Chloramphenicol acetyltransferase inactivates chloramphenicol by acetylating it using acetylcoenzyme A as the acetyl group donor. A family of enzymes is known to catalyze the mono-or dimethylation of the N-6 amino group of adenine in a highly conserved region of 23S rRNA, which may be involved directly in the formation of peptidyltransferase centers.

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5
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Figures

Image of Figure 5.1
Figure 5.1

(a) Hypothetical structure and mechanism of the transporter. In the cytoplasmic membrane in gram-positive bacteria (left), drugs enter unhindered and are pumped out into the medium. In gram-negative bacteria, drug molecules that have traversed the OM via porin channels or through its bilayer domain are extruded into the periplasmic space. (b) Complex efflux machinery that occurs only in gram-negative bacteria. The drug molecules are captured and pumped out directly into the medium by an assembly that contains, in addition to the pump, an OM channel and a membrane fusion protein. In both panels a and b, efflux of the drug molecules from the cytoplasm may occur, but it is not shown in the diagram for reasons of simplicity. LPS, lipopolysaccharide. Reprinted from H. Nikaido, Curr. Opin. Microbiol. 1:516–523, 1998, with permission from the publisher.

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5
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Image of Figure 5.2
Figure 5.2

Decreased accumulation of antibacterials and overcoming resistance due to it.

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5
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Image of Figure 5.3
Figure 5.3

Drug inactivation and overcoming resistance due to it.

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5
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Image of Figure 5.4
Figure 5.4

Target alteration.

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5
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References

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Tables

Generic image for table
Table 5.1

Characteristics of different elements involved in the spread of resistance genes

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5
Generic image for table
Table 5.2

Some examples of bacterial multidrug efflux transporters in gram-positive and gram-negative bacteria a

Citation: Mascaretti O. 2003. Mechanisms of Bacterial Resistance to the Action of Antibacterial Agents, p 87-96. In Bacteria versus Antibacterial Agents. ASM Press, Washington, DC. doi: 10.1128/9781555817794.ch5

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