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Quorum Sensing and Biofilm Disrupting Potential of Imidazole Derivatives in Chromobacterium violaceum Using Antimicrobial and Drug Discovery Approaches

  • Bacterial and Fungal Pathogenesis - Research Paper
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Abstract

Population of drug-resistant bacteria have increased at an alarming rate in the past few decades. The major reason for increasing drug resistance is the lack of new antibiotics and limited drug targets. It has therefore been a vital task to develop new antibiotics with different drug targets. Two such targets are biofilm formation and quorum sensing. Quorum sensing is cell to cell communication used by bacteria that initiates many important survival processes and aids in establishing pathogenesis. Both biofilm and quorum sensing are inter-related processes and play a major role in physiological and pathogenesis processes. In this study, five novel imidazole derivatives (IMA-1–IMA-5) were synthesised and tested for their antibacterial and anti-quorum sensing activities against Chromobacterium violaceum using different in silico and in vitro techniques following the standard protocols. In silico results revealed that all compounds were able to effectively bind to and interact sufficiently with the target protein CviR. CviR is a protein to which autoinducers bind to initiate the quorum sensing process. In silico results also revealed that the compounds generated favourable structural dynamics implying that the compounds would be able to effectively bind to CviR and inhibit quorum sensing. Susceptibility results revealed that IMA-1 is the most active of all the derivatives against both planktonic cells and biofilms. Qualitative and quantitative evaluation of anti-quorum sensing activity at sub-inhibitory concentrations of these compounds also revealed high activity for IMA-1. Down-regulation of most of the quorum sensing genes when cells were treated with the test compounds affirmed the high anti-quorum sensing activities of these compounds. The results from this study are promising and urges on the use of anti-quorum sensing and biofilm disrupting molecules to combat multi-drug resistance problem.

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Funding

AA acknowledges grant support from the South African National Research Foundation (NRF) Research Development Grant for Y-Rated Researchers (RDYR180418322304; Grant No: 116339) and University Research Committee Grant for 2019—Friedel Sellschop Award (Grant No: AZMD019).

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Authors and Affiliations

  1. Clinical Microbiology and Infectious Diseases, School of Pathology, Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa

    Madison Arendse, Shama Khan & Aijaz Ahmad

  2. Department of Chemistry, College of Science, University of Jeddah, Jeddah, 21589, Kingdom of Saudi Arabia

    Mohmmad Younus Wani, Faisal Mohammed Aqlan & Abdullah Saad Al-Bogami

  3. Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, 2193, South Africa

    Aijaz Ahmad

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  1. Madison Arendse
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  2. Shama Khan
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  3. Mohmmad Younus Wani
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  4. Faisal Mohammed Aqlan
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  5. Abdullah Saad Al-Bogami
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Contributions

AA, MYW, and SK designed the study. MYW, FA, and AAB performed the chemistry experiments. MT conducted the in vitro and in silico studies. MT, MYW, and FA wrote the manuscript’s. AA, AAB, and SK edited and approved the final manuscript. AA supervised the project and contributed to the reagents and bioinformatic tools. All authors read and approved the final manuscript.

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Correspondence to Mohmmad Younus Wani or Aijaz Ahmad.

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Key Points

• Five newly synthesised imidazole-based compounds were tested in silico and in vitro against Chromobacterium violaceum

• All compounds inhibited growth, quorum sensing and biofilm formation of Chromobacterium violaceum

• Quorum sensing of Chromobacterium violaceum was inhibiting at gene level

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Arendse, M., Khan, S., Wani, M.Y. et al. Quorum Sensing and Biofilm Disrupting Potential of Imidazole Derivatives in Chromobacterium violaceum Using Antimicrobial and Drug Discovery Approaches. Braz J Microbiol 53, 565–582 (2022). https://doi.org/10.1007/s42770-022-00702-8

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