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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.

Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics