Antibiotic drug discovery: Challenges and perspectives in the light of emerging antibiotic resistance

Adv Genet. 2020:105:229-292. doi: 10.1016/bs.adgen.2019.12.002. Epub 2020 May 6.

Abstract

Amid a rising threat of antimicrobial resistance in a global scenario, our huge investments and high-throughput technologies injected for rejuvenating the key therapeutic scaffolds to suppress these rising superbugs has been diminishing severely. This has grasped world-wide attention, with increased consideration being given to the discovery of new chemical entities. Research has now proven that the relatively tiny and simpler microbes possess enhanced capability of generating novel and diverse chemical constituents with huge therapeutic leads. The usage of these beneficial organisms could help in producing new chemical scaffolds that govern the power to suppress the spread of obnoxious superbugs. Here in this review, we have explicitly focused on several appealing strategies employed for the generation of new chemical scaffolds. Also, efforts on providing novel insights on some of the unresolved questions in the production of metabolites, metabolic profiling and also the serendipity of getting "hit molecules" have been rigorously discussed. However, we are highly aware that biosynthetic pathway of different classes of secondary metabolites and their biosynthetic route is a vast topic, thus we have avoided discussion on this topic.

Keywords: Cell signaling; Chemical analogs; Hit molecules; Metabolic switch; Molecular dialogs; Secondary metabolites.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / toxicity
  • Bacteria / metabolism
  • Drug Discovery / methods*
  • Drug Resistance, Microbial / genetics*
  • Epigenesis, Genetic / drug effects
  • Fungi / metabolism
  • Humans
  • Metabolome / drug effects*
  • Mutagenesis
  • Plants / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Stress, Physiological / drug effects

Substances

  • Anti-Bacterial Agents