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Research Ideas and Outcomes
Article . 2023 . Peer-reviewed
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Research Ideas and Outcomes
Article . 2023
Data sources: DOAJ
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https://dx.doi.org/10.60692/96...
Other literature type . 2023
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Other literature type . 2023
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Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics

استهداف بروتيوس ميرابيليس بروتينات مجمع بام لتطوير مضادات حيوية جديدة
Authors: Raphael Abban; Kwabena Sarpong; Samuel Duodu; Lydia Mosi; Abiola Isawumi;

Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics

Abstract

Urinary tract infections (UTIs) are frequent hospital-acquired infection, with Escherichia coli and Proteus mirabilis accounting for 90% of complicated UTIs. Emergence of multidrug-resistant (MDR) bacteria have complicated the treatment UTIs. P. mirabilis related UTIs has been associated with the production of urinary stones and long-term infections in patients with catheters. P. mirabilis and other uropathogens constitute a largely unexplored pathogen group. The pathogen is resistant to most antibiotics as a result of its impermeable outer membrane (OM). The β-barrel assemble machinery folds and inserts outer membrane proteins; however, there are no antibiotics targeting the OM assemble in clinical use currently. Therefore, this study seeks to identify drugs that will inhibit the activity of P. mirabilis B complex proteins and also determine their effects on P. mirabilis OM biogenesis. This would be achieved by screening approved drugs against the P. mirabilis Bam complex using computer-based in silico screening and cellular-based assays. First, the binding effects of drugs on P. mirabilis B complex proteins will be determined using docking algorithms. The antimicrobial and antivirulence activity of selected drugs from in silico analysis will be screened against MDR P. mirabilis. Finally, the effect of active drug(s) on the OM biogenesis of wild-type P. mirabilis and mutant P. mirabilis will be determined using peptide nucleic acids (PNA). Western lot analysis will be used to determine the abundance of proteins involved in OM biogenesis. Successful completion of this study will lead to the identification of novel antibiotics against MDR P. mirabilis and associated mechanisms while providing the foundation for future research endeavours on other uropathogens.

Keywords

Staphylococcus aureus, Epidemiology, Science, FOS: Basic medicine, Negibacteria, outer membrane, Microbiology, Biochemistry, Gene, antibiotics, Global Challenge of Antibiotic Resistance in Bacteria, Epidemiology and Treatment of Urinary Tract Infections, rinary tract infections, Endocrinology, Enterobacteriaceae, Antibiotics, Biochemistry, Genetics and Molecular Biology, Proteobacteria, Health Sciences, Escherichia coli, Genetics, Pathogenesis and Virulence of Escherichia coli, Proteus mirabilis, Biology, Bacterial outer membrane, Enterobacteriales, β-barrel assemble machinery, Bacteria, Peptide Nucleic Acid, Q, In silico, <i>Proteus mirabilis</i>, Life Sciences, bacterial invasion, Proteus, Biota, urinary stones, FOS: Biological sciences, Urinary Tract Infections, Medicine, Molecular Medicine, Gammaproteobacteria

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
Green
gold