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Marine-Derived Cytosine Arabinoside (Ara-C) Inhibits Biofilm Formation by Inhibiting PEL Operon Proteins (Pel A and Pel B) of Pseudomonas aeruginosa: An In Silico Approach

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Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a gram-negative biofilm-forming opportunistic human pathogen whose vital mechanism is biofilm formation for better survival. PelA and PelB proteins of the PEL operon are essential for bacterial-synthesized pellicle polysaccharide (PEL), which is a vital structural component of the biofilm. It helps in adherence of biofilm on the surface and maintenance of cell-to-cell interactions and with other matrix components. Here, in-silico molecular docking and simulation studies were performed against PelA and PelB using ten natural bioactive compounds, individually [podocarpic acids, ferruginol, scopadulcic acid B, pisiferic acid, metachromin A, Cytarabine (cytosine arabinoside; Ara-C), ursolic acid, oleanolic acid, maslinic acid, and betulinic acid], those have already been established as anti-infectious compounds. The results obtained from AutoDock and Glide-Schordinger stated that a marine-derived cytosine arabinoside (Ara-C) among the ten compounds binds active sites of PelA and PelB, exhibiting strong binding affinity [Trp224 (hydrogen), Ser219 (polar), Val234 (hydrophobic) for PelA; Leu365 and Glu389 (hydrogen), Gln366 (polar) for PelB] with high negative binding energy − 5.518 kcal/mol and − 6.056 kcal/mol, respectively. The molecular dynamic and simulation studies for 100 ns showed the MMGBSA binding energy scores are − 16.4 kcal/mol (Ara-C with PelA), and − 22.25 kcal/mol (Ara-C with PelB). Further, ADME/T studies indicate the IC50 values of AraC are 6.10 mM for PelA and 18.78 mM for PelB, which is a comparatively very low dose. The zero violation of Lipinski’s Rule of Five further established that Ara-C is a good candidate for drug development. Thus, Ara-C could be considered a potent anti-biofilm compound against PEL operon-dependent biofilm formation of P. aeruginosa.

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The datasets used and/or analyzed of the current study are included in the article. Further inquiries can be directed to the corresponding authors via email request.

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Acknowledgements

SD is grateful to the Nationa Institute of Technology-Agartala for providing the PhD fellowship. All authors express their profound gratitude to Dr. Amaresh Kumar Sahoo, Department of Applied Sciences, Indian Institute of Information Technology-Allahabad, for providing the dry laboratory facilities to accomplish this research work.

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  1. Department of Chemical Engineering, National Institute of Technology - Agartala, Agartala, Tripura, India

    Susmita Datta & Soma Nag

  2. Centre for Biotechnology, School of Pharmaceutical Sciences, Siksha ‘O’ Anusandhan (Deemed to be university), Bhubaneswar, Odisha, India

    Vishal Singh

  3. Department of Biotechnology, National Institute of Technology - Raipur, Raipur, Chhattisgarh, India

    Dijendra Nath Roy

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  1. Susmita Datta
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Datta, S., Singh, V., Nag, S. et al. Marine-Derived Cytosine Arabinoside (Ara-C) Inhibits Biofilm Formation by Inhibiting PEL Operon Proteins (Pel A and Pel B) of Pseudomonas aeruginosa: An In Silico Approach. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01169-8

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