High-Throughput Screening of Biodiversity for Antibiotic Discovery
The increasing number of infections caused by antibiotic-resistant strains of pathogens challenges modern technologies of drug discovery. Combinatorial chemistry approaches are based on chemical libraries. They enable the creation of high-affinity low-molecular-weight ligands of the therapeutically significant molecular targets of human cells, thus opening an avenue toward a directed design of highly effective therapeutic agents. Nevertheless, these approaches face insurmountable difficulties in antibiotic discovery. Natural compounds that have evolved for such important characteristics as broad specificity and efficiency are a good alternative to chemical libraries. However, unrestricted use of natural antibiotics and their analogues leads to avalanche-like spread of resistance among bacteria. The search for new natural antibiotics, in its turn, is extremely complicated nowadays by the problem of antibiotic rediscovery. This calls for the application of alternative high-throughput platforms for antibiotic activity screening, cultivation of “unculturable” microorganisms, exploration of novel antibiotic biosynthetic gene clusters, as well as their activation and heterologous expression. Microfluidic technologies for the screening of antibiotic activity at the level of single cells are, therefore, of great interest, since they enable the use of a single platform to combine the technology of ultrahigh-throughput screening, next-generation sequencing, and genome mining, thus opening up unique opportunities for antibiotic discovery.