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Chapter 13 : The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development

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The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, Page 1 of 2

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Abstract:

One might argue that the existence of the modern pharmaceutical industry relies on the discovery of compounds first identified by their ability to inhibit the growth of bacteria on agar (e.g., sulfonamides and penicillin). Some, including the authors, argue that the new technologies are not yet mature enough to deliver antibacterials, especially given the safety hurdles for antibacterials (currently marketed products are among the safest ever produced) and the desire for broad-spectrum activity expressed by the marketers and many physicians. An extension of the concept of essential gene targeting is the idea of attacking an essential metabolic pathway. The potential advantages of such a strategy for avoidance of the emergence of resistance are obvious. A number of approaches to this have been elucidated and are discussed in this chapter. The chapter examines the issue of virulence functions as targets. The concept of protein-protein interactions as drug targets has been a controversial one in the pharmaceutical industry. The distinctive nature of virulence inhibition as a method to eradicate bacterial infection will likely require special tools in the drug development process. The topic of enzyme inhibitors as antibacterial therapeutics must be taken in the context of an overall decrease in the effort to discover such therapies in the pharmaceutical industry. Given the difficulties outlined in the chapter, the challenge for researchers to meet the demands of physicians and their patients for therapies for infections increasingly caused by resistant pathogens becomes all that much greater.

Citation: Shlaes D, Alksne L, Projan S. 2007. The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, p 217-225. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch13

Key Concept Ranking

Fatty Acid Biosynthesis
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High-Performance Liquid Chromatography
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Figures

Image of Figure 13.1
Figure 13.1

Transcriptional profiling of the fatty acid biosynthesis pathway in ( ), using cells exposed to the inhibitor cerulenin (0.5 μg/ml [0.06× MIC] for 30 min) or untreated.

Citation: Shlaes D, Alksne L, Projan S. 2007. The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, p 217-225. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch13
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Image of Figure 13.2
Figure 13.2

Construction of a reporter assay for inhibitors of the fatty acid biosynthesis pathway ( ).

Citation: Shlaes D, Alksne L, Projan S. 2007. The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, p 217-225. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch13
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Image of Figure 13.3
Figure 13.3

Schematic representation of interacting proteins in the septal ring of .

Citation: Shlaes D, Alksne L, Projan S. 2007. The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, p 217-225. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch13
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Image of Figure 13.4
Figure 13.4

Sortase activity results in the transpeptidation of an MSCRAMM protein with its LPXTG motif to the cross-bridge of the gram-positive bacterial peptidoglycan.

Citation: Shlaes D, Alksne L, Projan S. 2007. The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, p 217-225. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch13
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Tables

Generic image for table
Table 13.1

Validation of protein-protein interactions as an antibacterial target

Citation: Shlaes D, Alksne L, Projan S. 2007. The Pharmaceutical Industry and Inhibitors of Bacterial Enzymes: Implications for Drug Development, p 217-225. In Bonomo R, Tolmasky M (ed), Enzyme-Mediated Resistance to Antibiotics. ASM Press, Washington, DC. doi: 10.1128/9781555815615.ch13

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