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Published on: January 8, 2014
Astaxanthin-Mediated Bacterial Lethality: Evidence from Oxidative Stress Contribution and Molecular Dynamics
Jamiu Olaseni Aribisala1, Sonto Nkosi1, Kehinde Idowu1
1Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban, South Africa.
Abstract:
The involvement of cellular oxidative stress in antibacterial therapy has remained a topical issue over the years. In this study, the contribution of oxidative stress to astaxanthin-mediated bacterial lethality was evaluated in silico and in vitro. For the in vitro analysis, the minimum inhibitory concentration (MIC) of astaxanthin was lower than that of novobiocin against Staphylococcus aureus but generally higher than those of the reference antibiotics against other test organisms. The level of superoxide anion of the tested organisms increased significantly following treatment with astaxanthin when compared with DMSO-treated cells. This increase compared favorably with those observed with the reference antibiotics and was consistent with a decrease in the concentration of glutathione (GSH) and corresponding significant increase in ADP/ATP ratio. These observations are suggestive of probable involvement of oxidative stress in antibacterial capability of astaxanthin and in agreement with the results of the in silico evaluations, where the free energy scores of astaxanthins' complexes with topoisomerase IV ParC and ParE were higher than those of the reference antibiotics. These observations were consistent with the structural stability and compactness of the complexes as astaxanthin was observed to be more stable against topoisomerase IV ParC and ParE than DNA Gyrase A and B. Put together, findings from this study underscored the nature and mechanism of antibacterial action of astaxanthin that could suggest practical approaches in enhancing our current knowledge of antibacterial arsenal and aid in the novel development of alternative natural topo2A inhibitor.
Insights
Astaxanthin exhibits antibacterial properties by inducing cellular oxidative stress, evidenced by increased superoxide anion and altered energy levels. This natural compound shows promise as a potential alternative antibacterial agent.
Area of Science:
- Microbiology
- Biochemistry
- Computational Biology
Background:
- Cellular oxidative stress is a key factor in antibacterial therapy.
- Astaxanthin's antibacterial mechanisms, particularly its link to oxidative stress, require further elucidation.
Purpose of the Study:
- To investigate the role of oxidative stress in astaxanthin's antibacterial activity against bacteria.
- To compare astaxanthin's efficacy and mechanism with reference antibiotics using in silico and in vitro methods.
Main Methods:
- Minimum Inhibitory Concentration (MIC) determination for astaxanthin and reference antibiotics.
- Measurement of superoxide anion levels, glutathione (GSH) concentration, and ADP/ATP ratio in treated bacterial cells.
- In silico analysis of astaxanthin's binding affinity and stability with bacterial topoisomerase targets.
Main Results:
- Astaxanthin treatment increased superoxide anion levels and the ADP/ATP ratio, while decreasing GSH concentration, indicating oxidative stress.
- In silico studies showed favorable binding energy scores for astaxanthin with topoisomerase IV (ParC and ParE) compared to reference antibiotics.
- Astaxanthin demonstrated greater stability against topoisomerase IV than DNA Gyrase.
Conclusions:
- Oxidative stress is a significant contributor to astaxanthin's antibacterial lethality.
- Astaxanthin acts as a natural topoisomerase inhibitor, offering a potential new avenue for antibacterial drug development.
