Efficacy of antimicrobial peptide mimics against staphylococcus infections
Abstract/Contents
- Abstract
- Staphylococcus aureus is one of the most common pathogens isolated from infected wounds, and significantly increases the cost of chronic wound treatment. Treatment with conventional antibiotics has been gradually rendered ineffective by the emergence of resistant pathogenic strains, e.g. methicillin-resistant Staphylococcus aureus (MRSA). Therefore, creating new antibiotics that use novel mechanisms and are challenging for pathogens to develop resistance to, is urgently required. One of the most promising candidates for the treatment of resistant infections are non-natural AMP mimics, formed by poly-n-substituted glycines, also called "peptoids". Antimicrobial peptoids developed in the Barron laboratory are mimics of naturally occurring host defence molecules, and have shown significant activity against a broad spectrum of bacteria, and therefore, were studied as a new generation of antimicrobial therapeutic agents against S. aureus infections. The peptoids showed highly significant activity against planktonic growth, impairment of existing biofilms, and prevention of biofilm formation for three strains of S. aureus - two non-resistant strains of S. aureus (Xen 36 and Xen 29), and one strain of MRSA. Compared to conventional antibiotics, the peptoids were particularly effective against MRSA. Among the peptoids studied, Peptoid 1, showed the highest tendency to form oligomers, possibly contributing to its high antimicrobial activity. Peptoids that are delivered as oligomers probably form a local accumulation of peptoids and improve their bioavailability onto the bacterial cell surface. Furthermore, the peptoids preferentially formed multimeric structures when in PBS solution, rather than water solution, results confirmed by analytical ultracentrifugation experiments. In addition, synergistic effects in antimicrobial activity against S. aureus were discovered when using combinations of peptoids, peptides and conventional antibiotics. Finally, the selected peptoids were tested for efficacy in a bioluminescent S. aureus mouse incision wound model, where it was observed that the peptoid-treated wounds completely cleared the infection within eight days, while the control wounds were still partially infected. It was discovered that Peptoid 1 delivered in PBS buffer in vivo gave better than an 8-fold better response than when delivered in water (as PBS was shown to facilitate multimerization). These observations demonstrate the promising potential of antimicrobial peptoids in the treatment of S. aureus wound infections.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Didwania, Maruti |
|---|---|
| Associated with | Stanford University, Department of Bioengineering. |
| Primary advisor | Cochran, Jennifer R |
| Primary advisor | Contag, Christopher H |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Contag, Christopher H |
| Thesis advisor | Blevins, Nikolas H |
| Thesis advisor | Covert, Markus |
| Advisor | Blevins, Nikolas H |
| Advisor | Covert, Markus |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Maruti Didwania. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Maruti Kumar Didwania
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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