Cellulase exhibited a therapeutic potential to inhibit Salmonella enterica serovar Typhi biofilm by targeting multiple regulatory proteins of biofilm.

Autor: Upadhyay A; Department of Biotechnology, National Institute of Technology, Raipur, 492010, (CG), India., Pal D; Department of Chemical Engineering, National Institute of Technology, Raipur, 492010, (CG), India. Electronic address: dpsingh.che@nitrr.ac.in., Kumar A; Department of Biotechnology, National Institute of Technology, Raipur, 492010, (CG), India. Electronic address: drawanishkr@gmail.com.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2024 Nov; Vol. 196, pp. 106979. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1016/j.micpath.2024.106979
Abstrakt: Biofilm-mediated Salmonella enterica serovar Typhi (Salmonella Ser. Typhi) infections are a growing global health issue due to the formation of antibiotic resistance. The study aimed to discover some of the druggable target proteins of Salmonella Ser. Typhi biofilm and antibiofilm enzyme to prevent Salmonella Ser. Typhi biofilm-mediated infection. Enzymatic therapy has demonstrated effective therapeutic results against bacterial infections due to its specificity and high binding capacity to the target. Therefore, this study focused on the computational interaction between the cellulase enzyme and Salmonella Ser. Typhi biofilm targets proteins with help of the various computational experiments such as ADMET (absorption, distribution, metabolism, excretion, and toxicity), protein-protein interactions, MMGBSA, etc. Further, in vitro validations of the typhoidal biofilm and cellulose presence in Salmonella Ser. Typhi biofilm was conducted using Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy, and Raman analysis. Additionally, a minimum biofilm inhibitory concentration assay for cellulase was conducted and find out the optimized cellulase concentration which showed its inhibitory effect on the Salmonella Ser. Typhi. The cellulase antibiofilm effect was analyzed with the help of SEM analysis. Further, the cellulose content in Salmonella Ser. Typhi was quantified before and after treatment of cellulase enzyme. As a result, 58.82 % cellulose content was decreased due to cellulase treatment in Salmonella Ser. Typhi. From the seven selected typhoidal biofilm regulatory proteins of Salmonella Ser. Typhi, we identified only five potential druggable targets: BcsA, CsgE, OmpR, CsgF, and CsgD. The BcsA protein is responsible for cellulose production in Salmonella Ser. Typhi biofilm. Consequently, cellulose worked as a fascinating drug target in Salmonella Ser. Typhi biofilm. Therefore, we used cellulase as a potential antibiofilm enzyme for target-based disruption of biofilm. The cellulase showed a high binding affinity with all five identified target proteins [BcsA(-205.62 kcal/mol) > CsgE(-108.20 kcal/mol) > OmpR(-107.58 kcal/mol) > CsgF(-73.74 kcal/mol) > CsgD(-66.61 kcal/mol)] in the protein-protein interaction analysis. Our computational analysis suggests that the cellulase enzyme may be used as a potential antibiofilm enzyme against Salmonella Ser. Typhi biofilm.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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