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Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli

  • Applied microbial and cell physiology
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Abstract

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3′,4,′5′-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

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Acknowledgments

Fellowship to GRD from Council of Scientific and Industrial Research (CSIR), New Delhi is gratefully acknowledged. The help of Dr. Mastan Singh and Dr M.K. Gupta, King George Medical University, and Lucknow in terms of providing multidrug-resistant clinical isolates of E. coli is gratefully acknowledged.

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Author notes

  1. Gaurav Raj Dwivedi

    Present address: School of Environmental Science, Babasaheb Bhim Rao Ambedkar University, Lucknow, 226025, UP, India

  2. Sudeep Roy

    Present address: Department of Biomedical Engineering, Faculty of Electronics and Communication, Brno University of Technology, Antonínská 548/1, 60190, Brno, Czech Republic

Authors and Affiliations

  1. Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India

    Gaurav Raj Dwivedi, Nimisha Tiwari, Akhil Kumar, Sudeep Roy, Anirban Pal, Debabrata Chanda, Ashok Sharma & Mahendra P. Darokar

  2. Chemical Sciences Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Near Kukrail Picnic Spot, P.O. CIMAP, Lucknow, 226015, India

    Aastha Singh & Arvind Singh Negi

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This study received financial support from Council of Scientific and Industrial Research under major laboratory project (MLP-02) and CSIR Network projects BSC 0121/BSC0203.

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Dwivedi, G.R., Tiwari, N., Singh, A. et al. Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli . Appl Microbiol Biotechnol 100, 2311–2325 (2016). https://doi.org/10.1007/s00253-015-7152-6

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