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Determining the potential targets of silybin by molecular docking and its antibacterial functions on efflux pumps and porins in uropathogenic E. coli

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Abstract

Background

One of the causes of antibiotic resistance is the reduced accumulation of antibiotics in bacterial cells through pumping out the drugs. Silybin, a key component of the Silybum marianum plant, exhibits various beneficial properties, including anti-bacterial, anti-inflammatory, antioxidant, and hepatoprotective effects.

Methods and results

Clinical isolates of E. coli were procured from 17 Shahrivar Children’s Hospital in Rasht, Guilan, located in northern Iran. Their susceptibility to six antibiotics was assessed using disc diffusion and broth dilution (MIC) methods. The antibacterial effects of silybin-loaded polymersome nanoparticles (SPNs) were investigated with broth dilution (MIC) and biofilm assays. Molecular docking was utilized to evaluate silybin’s (the antibacterial component) binding affinity to efflux pumps, porins, and their regulatory elements. Additionally, qRT-PCR analysis explored the expression patterns of acrA, acrB, tolC, ompC, and ompF genes in both SPNs (sub-MIC) and ciprofloxacin (sub-MIC)-treated and untreated E. coli isolates. The combined use of SPNs and ciprofloxacin exhibited a notable reduction in bacterial growth and biofilm formation, in ciprofloxacin-resistant isolates. The study identified eight overlapping binding sites of the AcrABZ-TolC efflux pump in association with silybin, demonstrating a binding affinity ranging from −7.688 to −10.33 Kcal/mol. Furthermore, the qRT-PCR analysis showed that silybin upregulated AcrAB-TolC efflux pump genes and downregulated ompC and ompF porin genes in combination with ciprofloxacin in transcriptional level in uropathogenic E. coli.

Conclusions

Silybin, a safe herbal compound, exhibits potential in inhibiting antibiotic resistance within bacterial isolates, potentially through the regulation of gene expression and plausible binding to target proteins.

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, Rasht Branch, Islamic Azad University, P.O. Box: 41335-3516, Rasht, Iran

    Shirin Fekri Kohan, Maryam Bazgosha, Somayeh Adelifar, Arman Hafezolghorani Esfahani, Mahdi Shahriarinour & Najmeh Ranji

  2. Department of Biology, Faculty of Sciences, Lahijan Branch, Islamic Azad University, Rasht, Iran

    Alireza Nouhi Kararoudi

  3. Sanford School of Medicine, University of South Dakota, Vermillion, South Dakota, USA

    Fatemeh Ghaderi Barmi

  4. Department of Chemistry, Faculty of Sciences, Rasht Branch, Islamic Azad University, Rasht, Iran

    Reyhaneh Kouchakinejad

  5. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Ebrahim Barzegari

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  1. Shirin Fekri Kohan
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Contributions

Study conception and/or design: E.B., N. R., and M. S.; data processing, collection, perform experiment: S. F. K., A. N. K., M. B., S. A., A. H. E., and F. G. B.; analysis and interpretation of results: S. F. K., E. B., R. K., and N. R.; draft manuscript preparation, visualization: E.B., N. R., and M. S.; critical revision or editing of the article: E.B., M. S., and N. R.; final approval of the version to be published: E.B., M. S., and N. R.; supervision: E.B., M. S., and N.R.; funding acquisition: all authors.

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Correspondence to Mahdi Shahriarinour or Najmeh Ranji.

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Fekri Kohan, S., Nouhi Kararoudi, A., Bazgosha, M. et al. Determining the potential targets of silybin by molecular docking and its antibacterial functions on efflux pumps and porins in uropathogenic E. coli. Int Microbiol (2024). https://doi.org/10.1007/s10123-024-00488-9

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