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In vivo efficacy and synergistic interaction of 16α-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide, a clerodane diterpene from Polyalthia longifolia against methicillin-resistant Staphylococcus aureus

  • Applied microbial and cell physiology
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Abstract

The Staphylococcus aureus bacterium, a nosocomial pathogen often causing untreatable and lethal infection in patients, mutated to become resistant to all the first-line drugs. The present study details the potential of clerodane diterpene 16α-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide (CD) isolated from Polyalthia longifolia against methicillin-resistant S. aureus (MRSA) through in vitro and in vivo assays. Minimum inhibitory concentration (MIC) of CD exhibited significant anti-MRSA activity (15.625–31.25 mg/l) against reference strain and seven clinical isolates, while time kill assays at graded MICs indicated 2.78–9.59- and 2.9–6.18-fold reduction in growth of reference strain and clinical isolates of S. aureus, respectively. The combined effect of the CD and 7.5 % NaCl resulted in significant reduction in microbial count within 24 h, indicating the loss of the salt tolerance ability of S. aureus. Further, release of 260-nm absorbing material and flow cytometric analysis revealed an increased uptake of propidium iodide. These assays may indicate the membrane-damaging potential of CD. The molecule CD was found to interact synergistically with clinically used antibiotics (FICI ≤ 0.5) against all clinical isolates. In infected mice, CD significantly (P < 0.001) lowered the systemic microbial load in blood, liver, kidney, lung and spleen tissues and did not exhibit any significant toxicity at 100 mg/kg body weight.

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Acknowledgments

The authors are thankful to the Director of CSIR-CIMAP for the R&D facilities. We are grateful to Prof. K. N. Prasad, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India for providing the clinical isolates of methicillin-resistant S. aureus. The help from Dr. S. C. Singh, Taxonomy and Pharmacognosy Department, CSIR-CIMAP, Lucknow, India in identifying the plant is gratefully acknowledged. This work was part of in-house project MLP-14 of CSIR-CIMAP, Lucknow, India.

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  1. CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, 226 015, India

    Vivek Kumar Gupta, Surjeet Verma, Anirban Pal, Santosh Kumar Srivastava & Mahendra P. Darokar

  2. Department of Biochemistry, Banaras Hindu University, Varanasi, India

    Vivek Kumar Gupta & Pramod Kumar Srivastava

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  1. Vivek Kumar Gupta
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  2. Surjeet Verma
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  6. Mahendra P. Darokar
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Correspondence to Mahendra P. Darokar.

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Gupta, V.K., Verma, S., Pal, A. et al. In vivo efficacy and synergistic interaction of 16α-hydroxycleroda-3, 13 (14) Z-dien-15, 16-olide, a clerodane diterpene from Polyalthia longifolia against methicillin-resistant Staphylococcus aureus . Appl Microbiol Biotechnol 97, 9121–9131 (2013). https://doi.org/10.1007/s00253-013-5154-9

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