
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.
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
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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