High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery

Abstract

Due to the continued emergence of resistance and a lack of new and promising antibiotics, bacterial infection has become a major public threat. High-throughput screening (HTS) allows rapid screening of a large collection of molecules for bioactivity testing and holds promise in antibacterial drug discovery. More than 50% of the antibiotics that are currently available on the market are derived from natural products. However, with the easily discoverable antibiotics being found, finding new antibiotics from natural sources has seen limited success. Finding new natural sources for antibacterial activity testing has also proven to be challenging. In addition to exploring new sources of natural products and synthetic biology, omics technology helped to study the biosynthetic machinery of existing natural sources enabling the construction of unnatural synthesizers of bioactive molecules and the identification of molecular targets of antibacterial agents. On the other hand, newer and smarter strategies have been continuously pursued to screen synthetic molecule libraries for new antibiotics and new druggable targets. Biomimetic conditions are explored to mimic the real infection model to better study the ligand–target interaction to enable the designing of more effective antibacterial drugs. This narrative review describes various traditional and contemporaneous approaches of high-throughput screening of natural products and synthetic molecule libraries for antibacterial drug discovery. It further discusses critical factors for HTS assay design, makes a general recommendation, and discusses possible alternatives to traditional HTS of natural products and synthetic molecule libraries for antibacterial drug discovery.

High-throughput bacterial co-encapsulation in microfluidic gel beads for discovery of antibiotic-producing strains

“…This step eliminates the need for prior isolation of microorganisms, a time and resource-consuming activity during the process of antibacterial drug discovery. 49…”

Mpox (formerly monkeypox): pathogenesis, prevention, and treatment

“… 110 , 231 – 233 HTS of marketed drugs or clinically established medications has the potential to expedite the identification of antiviral agents, thus saving valuable time. 234 – 236 For instance, the potential antiviral drug ribavirin has demonstrated therapeutic effectiveness against Mpox infection. Similarly, the widely used EGFR inhibitor gefitinib has shown promising antiviral activity against Mpox virus in addition to its approved indication for late-stage non-small cell lung cancer.…”

The Battle Against Antibiotic Resistance: Novel Therapeutic Options for Acinetobacter baumannii

“…The Battle against Antibiotic Resistance: Novel Therapeutic Options for Acinetobacter… DOI: http://dx.doi.org/10.5772/intechopen.1003617 A. baumannii to azithromycin and colistin in combination [59,60]. Erythromycin, levamisole, chloroquine, and propranolol inhibit quorum sensing and virulence factors in A. baumannii [61,62].…”