Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>
The rise in antimicrobial resistant bacteria is limiting the number of effective treatments for bacterial infections. <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> are two of the pathogens with the highest prevalence of resistance, and with the greatest need for n...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/2/389 |
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| author | Kylen E. Ridyard Mariam Elsawy Destina Mattrasingh Darien Klein Janine Strehmel Carole Beaulieu Alex Wong Joerg Overhage |
| author_facet | Kylen E. Ridyard Mariam Elsawy Destina Mattrasingh Darien Klein Janine Strehmel Carole Beaulieu Alex Wong Joerg Overhage |
| author_sort | Kylen E. Ridyard |
| collection | DOAJ |
| description | The rise in antimicrobial resistant bacteria is limiting the number of effective treatments for bacterial infections. <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> are two of the pathogens with the highest prevalence of resistance, and with the greatest need for new antimicrobial agents. Combinations of antimicrobial peptides (AMPs) and antibiotics that display synergistic effects have been shown to be an effective strategy in the development of novel therapeutic agents. In this study, we investigated the synergy between the AMP LL-37 and various classes of antibiotics against <i>E. coli</i> and <i>P. aeruginosa</i> strains. Of the six antibiotics tested (ampicillin, tetracycline, ciprofloxacin, gentamicin, aztreonam, and polymyxin B (PMB)), LL-37 displayed the strongest synergy against <i>E. coli</i> MG1655 and <i>P. aeruginosa</i> PAO1 laboratory strains when combined with PMB. Given the strong synergy, the PMB + LL-37 combination was chosen for further examination where it demonstrated synergy against multidrug-resistant and clinical <i>E. coli</i> isolates. Synergy of PMB + LL-37 towards clinical isolates of <i>P. aeruginosa</i> varied and showed synergistic, additive, or indifferent effects. The PMB + LL-37 combination treatment showed significant prevention of biofilm formation as well as eradication of pre-grown <i>E. coli</i> and <i>P. aeruginosa</i> biofilms. Using the <i>Galleria mellonella</i> wax worm model, we showed that the PMB + LL-37 combination treatment retained its antibacterial capacities in vivo. Flow analyses were performed to characterize the mode of action. The results of the present study provide proof of principle for the synergistic response between LL-37 and PMB and give novel insights into a promising new antimicrobial combination against gram-negative planktonic and biofilm cells. |
| first_indexed | 2024-03-11T09:14:47Z |
| format | Article |
| id | doaj.art-2ec50854d49f4b65b25fc722a74ea035 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-11T09:14:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-2ec50854d49f4b65b25fc722a74ea0352023-11-16T18:44:21ZengMDPI AGAntibiotics2079-63822023-02-0112238910.3390/antibiotics12020389Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>Kylen E. Ridyard0Mariam Elsawy1Destina Mattrasingh2Darien Klein3Janine Strehmel4Carole Beaulieu5Alex Wong6Joerg Overhage7Department of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Biology, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, CanadaInstitute of Functional Interfaces, Karlsruhe Institute of Technology, 76344 Karlsruhe, GermanyDepartment of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Biology, Carleton University, Ottawa, ON K1S 5B6, CanadaDepartment of Health Sciences, Carleton University, Ottawa, ON K1S 5B6, CanadaThe rise in antimicrobial resistant bacteria is limiting the number of effective treatments for bacterial infections. <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> are two of the pathogens with the highest prevalence of resistance, and with the greatest need for new antimicrobial agents. Combinations of antimicrobial peptides (AMPs) and antibiotics that display synergistic effects have been shown to be an effective strategy in the development of novel therapeutic agents. In this study, we investigated the synergy between the AMP LL-37 and various classes of antibiotics against <i>E. coli</i> and <i>P. aeruginosa</i> strains. Of the six antibiotics tested (ampicillin, tetracycline, ciprofloxacin, gentamicin, aztreonam, and polymyxin B (PMB)), LL-37 displayed the strongest synergy against <i>E. coli</i> MG1655 and <i>P. aeruginosa</i> PAO1 laboratory strains when combined with PMB. Given the strong synergy, the PMB + LL-37 combination was chosen for further examination where it demonstrated synergy against multidrug-resistant and clinical <i>E. coli</i> isolates. Synergy of PMB + LL-37 towards clinical isolates of <i>P. aeruginosa</i> varied and showed synergistic, additive, or indifferent effects. The PMB + LL-37 combination treatment showed significant prevention of biofilm formation as well as eradication of pre-grown <i>E. coli</i> and <i>P. aeruginosa</i> biofilms. Using the <i>Galleria mellonella</i> wax worm model, we showed that the PMB + LL-37 combination treatment retained its antibacterial capacities in vivo. Flow analyses were performed to characterize the mode of action. The results of the present study provide proof of principle for the synergistic response between LL-37 and PMB and give novel insights into a promising new antimicrobial combination against gram-negative planktonic and biofilm cells.https://www.mdpi.com/2079-6382/12/2/389LL-37polymyxin Bantimicrobial resistancesynergyanti-biofilm<i>Pseudomonas aeruginosa</i> |
| spellingShingle | Kylen E. Ridyard Mariam Elsawy Destina Mattrasingh Darien Klein Janine Strehmel Carole Beaulieu Alex Wong Joerg Overhage Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> Antibiotics LL-37 polymyxin B antimicrobial resistance synergy anti-biofilm <i>Pseudomonas aeruginosa</i> |
| title | Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> |
| title_full | Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> |
| title_fullStr | Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> |
| title_full_unstemmed | Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> |
| title_short | Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i> |
| title_sort | synergy between human peptide ll 37 and polymyxin b against planktonic and biofilm cells of i escherichia coli i and i pseudomonas aeruginosa i |
| topic | LL-37 polymyxin B antimicrobial resistance synergy anti-biofilm <i>Pseudomonas aeruginosa</i> |
| url | https://www.mdpi.com/2079-6382/12/2/389 |
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