Assessment of Berberine as a Multi-target Antimicrobial: A Multi-omics Study for Drug Discovery and Repositioning

Abstract

Postgenomics drug development is undergoing major transformation in the age of multi-omics studies and drug repositioning. Rather than applications solely in personalized medicine, omics science thus additionally offers a better understanding of a broader range of drug targets and drug repositioning. Berberine is an isoquinoline alkaloid found in many medicinal plants. We report here a whole genome microarray study in tandem with proteomics techniques for mining the plethora of targets that are putatively involved in the antimicrobial activity of berberine against Escherichia coli. We found DNA replication/repair and transcription to be triggered by berberine, indicating that nucleic acids, in general, are among its targets. Our combined transcriptomics and proteomics multi-omics findings underscore that, in the presence of berberine, cell wall or cell membrane transport and motility-related functions are also specifically regulated. We further report a general decline in metabolism, as seen by repression of genes in carbohydrate and amino acid metabolism, energy production, and conversion. An involvement of multidrug efflux pumps, as well as reduced membrane permeability for developing resistance against berberine in E. coli was noted. Collectively, these findings offer original and significant leads for omics-guided drug discovery and future repositioning approaches in the postgenomics era, using berberine as a multi-omics case study.

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

“…Moreover, our data could help in depicting the molecular pathways governing the beneficial effects of a variety of plant derivatives used in traditional medicine [12, 54–56]. Finally, we have to keep in mind that the global effect of BBR derivatives is strictly dependent on the experimental conditions and cell line tested; to generalize the observation made on colon cancer cells, we aim to extend the analysis to cell lines derived from other tumor types, expressing p53 either wt or mutated.…”

Morphological and ultrastructural changes in bacterial cells as an indicator of antibacterial mechanism of action

“…Transcriptional arrays, for example, generate complex patterns of results that can be difficult to interpret [15,25]. A forerunner of the molecular biology approach was the examination of bacteria treated with test agent for changes to their morphology and ultrastructure [24].…”

Proteomics Analyses ofBacillus subtilisafter Treatment with Plumbagin, a Plant-Derived Naphthoquinone

“…Natural products often exhibit antimicrobial activity against a wide range of pathogenic microorganisms. Recent advanced high-throughput multi-omics approaches integrating genomics, proteomics, and metabolomics have effectively accelerated the growth of antimicrobial research (Karaosmanoglu et al, 2014;Plichta et al, 2012;Wecke and Mascher, 2011). In addition, several research groups have reported that bacterial cell division process is one of the exciting targets for the development of next-generation antibiotics due to its conserved nature among the prokaryotes.…”