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Chapter 7 : Natural and Producer Immunity versus Acquired Resistance

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Abstract:

Plasmid sized DNA elements can integrate into specific attachment sites on chromosomes to create antibiotic resistance islands, as found in serovar Typhimurium DT104 and methicillin-resistant (MRSA). This allows multiple resistance genes to be maintained together. All these routes ensure rapid spread and stable maintenance of collections of antibiotic resistance genes through bacterial populations. Many antibiotics such as mitomycin and vancomycin have been developed into approved antibacterial drugs and have MICs or sometimes 50% inhibitory concentrations, often in Petri plate assays, in the range of 1 µg/ml. Many observers have noted that antibiotic producers could be vulnerable to their own chemical weapons of destruction and must have worked out strategies for their own protection and immunity. Three strategies for self-resistance have been described in macrolide producers and presage acquired resistance mechanisms in human pathogens. This chapter provides examples that typify the kinds of acquired resistance mechanisms that have presumably been accumulated, some from the reservoir of these genes in producer organisms and some from evolution of housekeeping enzymes to new specificities, by soil bacteria in the hundreds of millions of years that they have coevolved with antibiotic-producing neighbors. The three methods of self-protection in macrolide antibiotic producers set the stage for the understanding of the three major strategies for bacterial resistance to antibiotics.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Figures

Image of Figure 7.1
Figure 7.1

Recent outbreaks of antibiotic-resistant bacteria in the United States over the 11- year period 1983–1994.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.2
Figure 7.2

Time course for development of resistance to cephalosporins by MRSA.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.3
Figure 7.3

Progression of bacterial populations in surgical patients from MSSA to MRSA to VRE in a three-week time frame. (From Schentag et al. [1998], with permission.).

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.4
Figure 7.4

Schematics of antibiotic efflux protein pumps: (A) general scheme; (B) function for lantibiotic efflux pumps.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.5
Figure 7.5

Structures of the macrolide antibiotics erythromycin A, oleandomycin, and tylosin.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.6
Figure 7.6

Enzymatic mono- and dimethylation of A in 23S rRNA in macrolide resistance. SAM, -adenosylmethionine; SAH, -adenosylhomocysteine.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.7
Figure 7.7

Strategy for self-protection by the oleandomycin producer: intracellular glucosylation to an inactive precursor of oleandomycin by OleI, export by the OleB pump, and extracellular reactivation by the glycosidase OleR.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Figure 7.8

Glycopeptide antibiotics.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Figure 7.9

Regulation of the , and genes allows cell wall restructuring to glycopeptide antibiotic insensitivity at the time of antibiotic biosynthesis.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.10
Figure 7.10

Mitomycin: (A) DNA cross-linking by bioreductive alkylation; (B) enzymatic reoxidation of dihydro mitomycin by McrA for self-protection.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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Image of Figure 7.11
Figure 7.11

Analogy between producer self-protection and bacterial resistance.

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
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References

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Tables

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Table 7.1

Bacterial resistance to various classes of clinically used antibiotics

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7
Generic image for table
Table 7.2

Antibiotic resistance genes found in MRSA

Citation: Walsh C. 2003. Natural and Producer Immunity versus Acquired Resistance, p 91-105. In Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555817886.ch7

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