Inhibiting multidrug resistant Shigella flexneri using comparative genomics guided In vitro and In silico screening

Abstract

Ethnopharmacological relevance

The Gram-negative bacterium Shigella is the most widely documented etiologic factor for diarrheal mortality in infants, contributing to 13.2 % of diarrheal episodes across the globe. The present surge in antibiotic resistance, increasing numbers of non-typeable strains, and the disparate regional distribution of multiple Shigella variants has rendered it obvious that novel therapeutic alternatives are desperately sought after to address the growing threat of shigellosis.

Aim of the study

In the present investigation, we have assessed the antibacterial properties of selected medicinal plants, against a naturally isolated, multidrug-resistant strain of Shigella flexneri, using different in-vitro susceptibility assays.

Materials and methods

We used virtual screening, molecular docking, and molecular dynamic simulation to quickly and accurately screen natural compounds derived from these plants for antibacterial agents. To further comprehend the antimicrobial mechanism of the herbal extracts and their active constituents against Shigella flexneri, a comparative transcriptome analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was undertaken to contrast and evaluate the differential patterns of gene expression between the treated and untreated populations.

Results

The findings deemed the two herbal extracts of Psidium guajava and Scoparia dulcis as a source of viable therapeutic candidates against the multi-drug-resistant strain.

Conclusions

The prospective active constituents, viz. 5-Hydroxy-1-isopropyl-6,6-dimethyl-5-phenyl-piperidin-2-one and limonene, and their corresponding therapeutic targets reported in this research, thus bring up the possibility of switching existing drugs with more potent phytopharmaceuticals for effectively controlling Shigella superbugs, awaiting further investigations.