14.7 – Current Strategies for Antimicrobial Discovery
14.7 – Current Strategies for Antimicrobial Discovery
Learning Objectives
- Describe the methods and strategies used for discovery of new antimicrobial agents.
With the continued evolution and spread of antimicrobial resistance, and now the identification of pan-resistant bacterial pathogens, the search for new antimicrobials is essential for preventing the postantibiotic era. Although development of more effective semisynthetic derivatives is one strategy, resistance to them develops rapidly because bacterial pathogens are already resistant to earlier-generation drugs in the family and can easily mutate and develop resistance to the new semisynthetic drugs. Today, scientists continue to hunt for new antimicrobial compounds and explore new avenues of antimicrobial discovery and synthesis. They check large numbers of soils and microbial products for antimicrobial activity by using high-throughput screening methods, which use automation to test large numbers of samples simultaneously. The recent development of the iChip[1] allows researchers to investigate the antimicrobial-producing capabilities of soil microbes that are difficult to grow by standard cultivation techniques in the laboratory. Rather than grow the microbes in the laboratory, they are grown in situ—right in the soil. Use of the iChip has resulted in the discovery of teixobactin, a novel antimicrobial from Mount Ararat, Turkey. Teixobactin targets two distinct steps in gram-positive cell wall synthesis and for which antimicrobial resistance appears not yet to have evolved.
Although soils have been widely examined, other environmental niches have not been tested as fully. Since 70% of the earth is covered with water, marine environments could be mined more fully for the presence of antimicrobial- producing microbes. In addition, researchers are using combinatorial chemistry, a method for making a very large number of related compounds from simple precursors, and testing them for antimicrobial activity. An additional strategy that needs to be explored further is the development of compounds that inhibit resistance mechanisms and restore the activity of older drugs, such as the strategy described earlier for β-lactamase inhibitors like clavulanic acid. Finally, developing inhibitors of virulence factor production and function could be a very important avenue. Although this strategy would not be directly antibacterial, drugs that slow the progression of an infection could provide an advantage for the immune system and could be used successfully in combination with antimicrobial drugs.
Check Your Understanding
- What are new sources and strategies for developing drugs to fight infectious diseases?
Eye on Ethics
The (Free?) Market for New Antimicrobials
There used to be plenty of antimicrobial drugs on the market to treat infectious diseases. However, the spread of antimicrobial resistance has created a need for new antibiotics to replace those that are no longer as effective as they once w