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Chapter 6 : Antibiotics That Inhibit the Synthesis of Bacterial Proteins

Authors: Abigail A. Salyers1, Dixie D. Whitt1
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Affiliations: 1: University of Illinois at Urbana-Champaign, Urbana, Illinois
Content Type: Trade
Publication Year: 2005

Category: General Interest; Bacterial Pathogenesis

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Abstract:

Bacteria need proteins to perform essential functions and to act as structural components of the cell. Thus, it is not surprising that the process of bacterial protein synthesis has been a major target for antibiotics. Mupirocin was ignored for years because it is too toxic for internal use. It has been used primarily as a topical antibiotic to eliminate antibiotic-resistant from the noses of hospital workers. Aminoglycosides are among the most widely used antibiotics. Streptomycin was one of the earliest antibiotics to enter the market, and it won its discoverer, Selman Waxman, a Nobel Prize. One way bacteria can become resistant to aminoglycosides is to mutate the ribosomal protein that provides the binding site for the antibiotic. The antibiotic no longer binds to the ribosome and thus no longer inhibits growth of the bacteria. Tetracycline, like streptomycin, binds to the small subunit of the bacterial ribosome. The tetracycline family, which includes such antibiotics as doxycycline, oxytetracycline, and demeclocycline, gets its name from its structure, which consists of four fused cyclic rings. The chapter describes three known mechanisms of resistance to tetracycline. Another widely used class of antibiotics is the macrolides. Erythromycin is an example of a macrolide. Erythromycin and other macrolides have had an excellent safety record, with few side effects. The chapter also talks about clindamycin, synercid, and oxazolidones.

Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6

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Bacterial Proteins
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Bacterial Pathogenesis
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Antibiotics That Inhibit the Synthesis of Bacterial Proteins
Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6
/content/10.1128/9781555817602.chap06.fig6-1
Figure 6.1

Structure of a ribosome. The bacterial ribosome is made up of two subunits, a 30S and a 50S subunit. The 30S subunit contains rRNA plus 31 ribosomal proteins. The 50S subunit contains rRNA plus 21 ribosomal proteins. The size of the complete ribosome (the 30S plus the 50S subunit) is 70S. (Reprinted from L. Snyder and W. Champness, , ASM Press, Washington, D.C., 1997.)

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Figure 6.1

Structure of a ribosome. The bacterial ribosome is made up of two subunits, a 30S and a 50S subunit. The 30S subunit contains rRNA plus 31 ribosomal proteins. The 50S subunit contains rRNA plus 21 ribosomal proteins. The size of the complete ribosome (the 30S plus the 50S subunit) is 70S. (Reprinted from L. Snyder and W. Champness, , ASM Press, Washington, D.C., 1997.)

Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6
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Figure 6.2

Overview of translation. After the tRNA containing methione (Met) binds to the start codon (A), the incoming tRNA bound to its amino acid (Leu) enters the A site on the 30S ribosome (B). (C) An enzyme on the 50S ribosome binds the next amino acid to the growing polypeptide. (D) The tRNA is moved to the P site, making room at the A site for another tRNA. Antibiotics that block various steps in translation are indicated.

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Image of Figure 6.2
Figure 6.2

Overview of translation. After the tRNA containing methione (Met) binds to the start codon (A), the incoming tRNA bound to its amino acid (Leu) enters the A site on the 30S ribosome (B). (C) An enzyme on the 50S ribosome binds the next amino acid to the growing polypeptide. (D) The tRNA is moved to the P site, making room at the A site for another tRNA. Antibiotics that block various steps in translation are indicated.

Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6
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Figure 6.3

Modification of aminoglycosides by attachment of chemical groups such as phosphoryl, acetyl, and adenyl. (Reprinted from A. A. Salyers and D. D. Whitt, , ASM Press, Washington, D.C., 2002.)

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Image of Figure 6.3
Figure 6.3

Modification of aminoglycosides by attachment of chemical groups such as phosphoryl, acetyl, and adenyl. (Reprinted from A. A. Salyers and D. D. Whitt, , ASM Press, Washington, D.C., 2002.)

Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6
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Figure 6.4

Mechanisms of tetracycline resistance. (A) Tetracycline (black squares) is taken up by a transporter (open ellipse); intracellular concentration becomes higher than extracellular concentration; tetracycline binds to ribosomes and stops protein synthesis. (B) Cytoplasmic membrane protein (open triangles) pumps tetracycline out of the cell as fast as the transporter takes it up; intracellular concentration remains too low for effective binding to ribosomes. (C) Tetracycline accumulation within the cell is similar to that in a sensitive cell, but the ribosome is protected (hatching), so tetracycline no longer binds to it. (Reprinted from A. A. Salyers and D. D. Whitt, , ASM Press, Washington, D.C., 2002.)

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10.1128/9781555817602/fig6-4.gif
Image of Figure 6.4
Figure 6.4

Mechanisms of tetracycline resistance. (A) Tetracycline (black squares) is taken up by a transporter (open ellipse); intracellular concentration becomes higher than extracellular concentration; tetracycline binds to ribosomes and stops protein synthesis. (B) Cytoplasmic membrane protein (open triangles) pumps tetracycline out of the cell as fast as the transporter takes it up; intracellular concentration remains too low for effective binding to ribosomes. (C) Tetracycline accumulation within the cell is similar to that in a sensitive cell, but the ribosome is protected (hatching), so tetracycline no longer binds to it. (Reprinted from A. A. Salyers and D. D. Whitt, , ASM Press, Washington, D.C., 2002.)

Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6
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References

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Tables

Antibiotics That Inhibit the Synthesis of Bacterial Proteins
Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6
/content/10.1128/9781555817602.chap06.tab6-1
Table 6.1

Widely used protein synthesis inhibitors and their brand names

Generic image for table
Table 6.1

Widely used protein synthesis inhibitors and their brand names

Citation: Salyers A, Whitt D. 2005. Antibiotics That Inhibit the Synthesis of Bacterial Proteins, p 66-82. In Revenge of the Microbes. ASM Press, Washington, DC. doi: 10.1128/9781555817602.ch6

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