Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics
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 pr...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Pensoft Publishers
2023-10-01
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| Series: | Research Ideas and Outcomes |
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| Online Access: | https://riojournal.com/article/106849/download/pdf/ |
| _version_ | 1797653917389029376 |
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| author | Raphael Abban Sarpong Kwabena Samuel Duodu Lydia Mosi Isawumi Abiola |
| author_facet | Raphael Abban Sarpong Kwabena Samuel Duodu Lydia Mosi Isawumi Abiola |
| author_sort | Raphael Abban |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T16:51:46Z |
| format | Article |
| id | doaj.art-d6a95e3e7aa24377a6e33328e5882090 |
| institution | Directory Open Access Journal |
| issn | 2367-7163 |
| language | English |
| last_indexed | 2024-03-11T16:51:46Z |
| publishDate | 2023-10-01 |
| publisher | Pensoft Publishers |
| record_format | Article |
| series | Research Ideas and Outcomes |
| spelling | doaj.art-d6a95e3e7aa24377a6e33328e58820902023-10-21T08:11:06ZengPensoft PublishersResearch Ideas and Outcomes2367-71632023-10-01911510.3897/rio.9.e106849106849Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel AntibioticsRaphael Abban0Sarpong Kwabena1Samuel Duodu2Lydia Mosi3Isawumi Abiola4University of Ghana, West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular BiologyUniversity of Ghana, Department of Biochemistry, Cell and Molecular Biology, LegonUniversity of Ghana, West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular BiologyUniversity of Ghana, West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology, LegonUniversity of Ghana, West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular BiologyUrinary 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.https://riojournal.com/article/106849/download/pdf/rinary tract infections<i>Proteus mirabilis</i> |
| spellingShingle | Raphael Abban Sarpong Kwabena Samuel Duodu Lydia Mosi Isawumi Abiola Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics Research Ideas and Outcomes rinary tract infections <i>Proteus mirabilis</i> |
| title | Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics |
| title_full | Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics |
| title_fullStr | Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics |
| title_full_unstemmed | Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics |
| title_short | Targeting Proteus mirabilis BAM Complex Proteins for Development of Novel Antibiotics |
| title_sort | targeting proteus mirabilis bam complex proteins for development of novel antibiotics |
| topic | rinary tract infections <i>Proteus mirabilis</i> |
| url | https://riojournal.com/article/106849/download/pdf/ |
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