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Anti-microbial and Anti-biofilm activity of a novel Dibenzyl (benzo[d] thiazol-2-yl (hydroxy) methyl) phosphonate by inducing protease expression in Staphylococcus aureus

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Abstract

In the present study a novel Dibenzyl (benzo[d]thiazol-2-yl(hydroxy)methyl) phosphonate (3b) derived from α-Hydroxyphosphonate exhibited anti-Staphylococcus aureus and anti-biofilm properties against penicillin, ampicillin and methicillin-resistant strains of S. aureus. The compound 3b showed Minimum inhibitory concentration (MIC90) at 160 ± 1 µg/ml and lethal dose (LD50) at 80 ± 1 µg/ml. S. aureus growing as planktonic culture shows a formation of aggregates which is the prerequisite for the formation of biofilms, the compound 3b disrupted aggregates and cleared all the preformed planktonic biofilms and prevented their recurrence. The SDS-PAGE analysis of compound 3b treated S. aureus showed gradual lysis of total proteins. The zymogram analysis indicated overexpression of proteases which is the principle reason for lysis of total proteins of S. aureus on incubation with compound 3b. Further, the dot blot analysis indicated complete lysis of Protein-A in the culture filtrate of all the drug-resistant strains of S. aureus a prominent virulence factor and biofilm forming protein. All these features exhibited by compound 3b makes it as a potential therapeutic molecule in the treatment of S. aureus infections.

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Acknowledgements

This study was supported by the Indian Council for Medical Research (ICMR), New Delhi, INDIA under Grant of Major Research Project of ICMR—SRF (Senior Research Fellowship), File No.80/849/2014-ECD-I, dated: 7-5-2014.; Sri Venkateswara Institute of Medical Sciences and University, under SBAVP scheme (SBAVP/Ph.D/03) dated: 9-10- 2012. This paper forms a part of Ph.D. thesis work going to be submitted to SVIMS University.

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Authors and Affiliations

  1. Department of Biotechnology, Sri Venkateswara Institute of Medical Sciences and University, Tirupati, 517507, Andhra Pradesh, India

    Sthanikam Yeswanth & Potukuchi Venkata Gurunadha Krishna Sarma

  2. Department of Chemistry, Sri Venkateswara University, Tirupati, 517501, Andhra Pradesh, India

    Kuruva Chandra Sekhar

  3. Department of Microbiology, Sri Venkateswara Institute of Medical Sciences and University, Tirupati, 517507, Andhra Pradesh, India

    Abhijit Chaudhary

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  1. Sthanikam Yeswanth
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  2. Kuruva Chandra Sekhar
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  3. Abhijit Chaudhary
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  4. Potukuchi Venkata Gurunadha Krishna Sarma
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Correspondence to Potukuchi Venkata Gurunadha Krishna Sarma.

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Yeswanth, S., Chandra Sekhar, K., Chaudhary, A. et al. Anti-microbial and Anti-biofilm activity of a novel Dibenzyl (benzo[d] thiazol-2-yl (hydroxy) methyl) phosphonate by inducing protease expression in Staphylococcus aureus . Med Chem Res 27, 785–795 (2018). https://doi.org/10.1007/s00044-017-2102-8

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