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Journal Article Research Support, Non-U.S. Gov't Epublish 3 citations

PubMed: 36429532 DOI: 10.3390/ijerph192214812

Integrated Pangenome Analysis and Pharmacophore Modeling Revealed Potential Novel Inhibitors against .

Int J Environ Res Public Health 19(22)

Authors: Mohammed S Almuhayawi, Soad K Al Jaouni, Samy Selim, Dalal Hussien M Alkhalifah, Romina Alina Marc, Sidra Aslam, Peter Poczai

Affiliations

  • Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • Department of Hematology/Oncology, Yousef Abdulatif Jameel Scientific Chair of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia.
  • Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
  • Food Engineering Department, Faculty of Food Science and Technology, University of Agricultural Science and Veterinary Medicine Cluj-Napoca, 3-5 Calea Mănă ̧stur Street, 400372 Cluj-Napoca, Romania.
  • Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Punjab 38000, Pakistan.
  • Banner Sun Health Research Institute, Sun City, AZ 85351, USA.
  • Botany Unit, Finnish Museum of Natural History, University of Helsinki, P.O. Box 7, FI-00014 Helsinki, Finland.

Abstract

is a novel, multidrug-resistant pathogen belonging to the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. However, there is currently no registered drug on the market that has been shown to be effective. Hence, there is an urgent need to identify novel therapeutic targets and effective treatments for . In the current study, a bacterial pan genome analysis and subtractive proteomics approach was employed to the core proteomes of six strains of using several bioinformatic tools, software, and servers. However, 2611 nonredundant proteins were predicted from the 21,720 core proteins of core proteome. Out of 2611 nonredundant proteins, 372 were obtained from Geptop2.0 as essential proteins. After the subtractive proteomics and subcellular localization analysis, only 133 proteins were found in cytoplasm. All cytoplasmic proteins were examined using BLASTp against the virulence factor database, which classifies 20 therapeutic targets as virulent. Out of these 20, 3 cytoplasmic proteins: ferric iron uptake transcriptional regulator (FUR), UDP-2,3diacylglucosamine diphosphatase (UDP), and lipid-A-disaccharide synthase (lpxB) were chosen as potential drug targets. These drug targets are important for bacterial survival, virulence, and growth and could be used as therapeutic targets. More than 2500 plant chemicals were used to molecularly dock these proteins. Furthermore, the lowest-binding energetic docked compounds were found. The top five hit compounds, , , , and demonstrated optimum binding against all three target proteins. Furthermore, molecular dynamics simulations and MM/GBSA analyses validated the stability of ligand-protein complexes and revealed that these compounds could serve as potential replication inhibitors. Consequently, this study marks a significant step forward in the creation of new and powerful drugs against . Future studies should validate these targets experimentally to prove their function in survival and virulence.

MeSH

Environmental Exposure, Pharmaceutical Preparations, Cytoplasm, Proteomics, Therapeutics, Proteome, Virulence, Infections

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