Redox-active compounds with a history of human use: antistaphylococcal action and potential for repurposing as topical antibiofilm agents
| Autor: | Jonathan H. Cove, Nicola Ooi, E. A. Eady, Alex J. O'Neill |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Microbiology (medical)
Staphylococcus aureus Staphylococcus Microbial Sensitivity Tests Biology medicine.disease_cause biofilm Microbiology 03 medical and health sciences chemistry.chemical_compound mode of action Staphylococcus epidermidis Drug Resistance Bacterial medicine Humans Pharmacology (medical) Mode of action Original Research 030304 developmental biology Pharmacology 0303 health sciences Microbial Viability 030306 microbiology Broth microdilution Biofilm Biofilm matrix biology.organism_classification Anti-Bacterial Agents antibacterial Infectious Diseases chemistry Celastrol Biofilms Mutation Anti-Infective Agents Local Gentamicin Oxidation-Reduction medicine.drug |
| Zdroj: | Journal of Antimicrobial Chemotherapy |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dku409 |
| Popis: | Objectives: To investigate the antistaphylococcal/antibiofilm activity and mode of action (MOA) of a panel of redox-active (RA) compounds with a history of human use and to provide a preliminary preclinical assessment of their potential for topical treatment of staphylococcal infections, including those involving a biofilm component. Methods: Antistaphylococcal activity was evaluated by broth microdilution and by time-kill studies with growing and slow- or non-growing cells. The antibiofilm activity of RA compounds, alone and in combination with established antibacterial agents, was assessed using the Calgary Biofilm Device. Established assays were used to examine the membrane-perturbing effects of RA compounds, to measure penetration into biofilms and physical disruption of biofilms and to assess resistance potential. A living skin equivalent model was used to assess the effects of RA compounds on human skin. Results: All 15 RA compounds tested displayed antistaphylococcal activity against planktonic cultures (MIC 0.25-128 mg/L) and 7 eradicated staphylococcal biofilms (minimum biofilm eradication concentration 4-256 mg/L). The MOA of all compounds involved perturbation of the bacterial membrane, whilst selected compounds with antibiofilm activity caused destructuring of the biofilm matrix. The two most promising agents [celastrol and nordihydroguaiaretic acid (NDGA)] in respect of antibacterial potency and selective toxicity against bacterial membranes acted synergistically with gentamicin against biofilms, did not damage artificial skin following topical application and exhibited low resistance potential. Conclusions: In contrast to established antibacterial drugs, some RA compounds are capable of eradicating staphylococcal biofilms. Of these, celastrol and NDGA represent particularly attractive candidates for development as topical antistaphylococcal biofilm treatments. |
| Databáze: | OpenAIRE |
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