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

Autor: Arendse M; Clinical Microbiology and Infectious Diseases, School of Pathology, Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa., Khan S; Clinical Microbiology and Infectious Diseases, School of Pathology, Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa., Wani MY; Department of Chemistry, College of Science, University of Jeddah, Jeddah, 21589, Kingdom of Saudi Arabia. mwani@uj.edu.sa., Aqlan FM; Department of Chemistry, College of Science, University of Jeddah, Jeddah, 21589, Kingdom of Saudi Arabia., Al-Bogami AS; Department of Chemistry, College of Science, University of Jeddah, Jeddah, 21589, Kingdom of Saudi Arabia., Ahmad A; Clinical Microbiology and Infectious Diseases, School of Pathology, Health Sciences, University of the Witwatersrand, Johannesburg, 2193, South Africa. mwani@uj.edu.sa.; Infection Control, Charlotte Maxeke Johannesburg Academic Hospital, National Health Laboratory Service, Johannesburg, 2193, South Africa. mwani@uj.edu.sa.
Jazyk: angličtina
Zdroj: Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] [Braz J Microbiol] 2022 Jun; Vol. 53 (2), pp. 565-582. Date of Electronic Publication: 2022 Mar 17.
DOI: 10.1007/s42770-022-00702-8
Abstrakt: 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.
(© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)
Databáze: MEDLINE
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