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Examine the characterization of biofilm formation and inhibition by targeting SrtA mechanism in Bacillus subtilis: a combined experimental and theoretical study

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Abstract

Bacillus subtilis is one of the well-known biofilm-forming organisms associated with plants, animals, and also used as a model organism for all Bacillus sp. In B. subtilis, SrtA enzyme plays the imperative roles in mechanism of signaling pathway and microbial adherence toward the host. SrtA is highly considered as a universal drug target for all Gram positive pathogens. Because of unresolved 3D structure of SrtA in Gram positive bacteria including B. subtilis, we developed a homology model protein using structural alignments of similar SrtA from B. anthracis. While the structural model of SrtA is analyzed because of its significance in biofilm formation by screening the suitable active site based compounds and analyzing the ability of bacterial biofilm inhibition. Druggability site based screening able to retrieve the active compounds against SrtA and checked the activity of the screened compounds through experimental biochemical assays and in situ microscopic analysis. Here in this study we concluded the computationally screened SrtA inhibitors showed high level of biofilm inhibition despite difficulties in bacterial membrane rigidification. Hence this study leads a way to the new compounds that may be useful to treat the bacterial infections

Figure

Bacillus subtilis is one of the well-known biofilm-forming organisms referred to as model organism for all gram positive pathogens. From this organism, the universal drug target SrtA is evaluated for its biofilm forming ability and inhibitors are screened against the same, through in silico and in vitro methods. Druggability region based SrtA inhibitors are successful by showing anti microbial and anti biofilm activity. This study shows prominent common SrtA inhibitors against the gram positive pathogens

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Abbreviations

B. subtilis:

Bacillus subtilis

B. anthracis:

Bacillus anthracis

SrtA:

Sortase A

MD simulation:

Molecular dynamics simulation

CLSM:

Confocal laser scanning microscopy

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Acknowledgments

The authors thankfully acknowledge the CSIR for research funding and fellowship grants (Ref. No: 37(1491)/11/EMR-II). One of the authors Chandrabose Selvaraj gratefully acknowledges CSIR for the Senior Research Fellowship (SRF). JSV gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), New Delhi for the financial assistance Rendered [Ref: 9/688 (0023)/2013, EMR-I]. Poonam Singh and Sanjeev Kumar Singh acknowledge CSIR-CDRI and Alagappa University for signing the Memorandum of Understanding.

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Authors and Affiliations

  1. Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, 630 004, Tamil Nadu, India

    Chandrabose Selvaraj & Sanjeev Kumar Singh

  2. Crustacean Molecular Biology & Genomics Lab, Department of Animal Health and Management, Alagappa University, Karaikudi, 630 004, Tamil Nadu, India

    Jeyachandran Sivakamavalli & Baskaralingam Vaseeharan

  3. Toxicology Division, Central Drug Research Institute, Lucknow, 226 001, Uttar Pradesh, India

    Poonam Singh

Authors
  1. Chandrabose Selvaraj
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  2. Jeyachandran Sivakamavalli
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  3. Baskaralingam Vaseeharan
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  4. Poonam Singh
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  5. Sanjeev Kumar Singh
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Correspondence to Sanjeev Kumar Singh.

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Selvaraj, C., Sivakamavalli, J., Vaseeharan, B. et al. Examine the characterization of biofilm formation and inhibition by targeting SrtA mechanism in Bacillus subtilis: a combined experimental and theoretical study. J Mol Model 20, 2364 (2014). https://doi.org/10.1007/s00894-014-2364-8

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