Vol 9: Photoinduced Membrane Damage of E. coli and S. aureus by the Photosensitizer-Antimicrobial Peptide Conjugate Eosin-KLAKLAK2.Report as inadecuate



 Vol 9: Photoinduced Membrane Damage of E. coli and S. aureus by the Photosensitizer-Antimicrobial Peptide Conjugate Eosin-KLAKLAK2.


Vol 9: Photoinduced Membrane Damage of E. coli and S. aureus by the Photosensitizer-Antimicrobial Peptide Conjugate Eosin-KLAKLAK2. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 9: Photoinduced Membrane Damage of E. coli and S. aureus by the Photosensitizer-Antimicrobial Peptide Conjugate Eosin-KLAKLAK2.
This article is from PLoS ONE, volume 9.AbstractBackground-Objectives: Upon irradiation with visible light, the photosensitizer-peptide conjugate eosin-KLAKLAK2 kills a broad spectrum of bacteria without damaging human cells. Eosin-KLAKLAK2 therefore represents an interesting lead compound for the treatment of local infection by photodynamic bacterial inactivation. The mechanisms of cellular killing by eosin-KLAKLAK2, however, remain unclear and this lack of knowledge hampers the development of optimized therapeutic agents. Herein, we investigate the localization of eosin-KLAKLAK2 in bacteria prior to light treatment and examine the molecular basis for the photodynamic activity of this conjugate. Methodology-Principal Findings: By employing photooxidation of 3,3-diaminobenzidine DAB, scanning transmission electron microscopy STEM, and energy dispersive X-ray spectroscopy EDS methodologies, eosin-KLAKLAK2 is visualized at the surface of E. coli and S. aureus prior to photodynamic irradiation. Subsequent irradiation leads to severe membrane damage. Consistent with these observations, eosin-KLAKLAK2 binds to liposomes of bacterial lipid composition and causes liposomal leakage upon irradiation. The eosin moiety of the conjugate mediates bacterial killing and lipid bilayer leakage by generating the reactive oxygen species singlet oxygen and superoxide. In contrast, the KLAKLAK2 moiety targets the photosensitizer to bacterial lipid bilayers. In addition, while KLAKLAK2 does not disrupt intact liposomes, the peptide accelerates the leakage of photo-oxidized liposomes. Conclusions-Significance: Together, our results suggest that KLAKLAK2 promotes the binding of eosin Y to bacteria cell walls and lipid bilayers. Subsequent light irradiation results in membrane damage from the production of both Type I & II photodynamic products. Membrane damage by oxidation is then further aggravated by the KLAKLAK2 moiety and membrane lysis is accelerated by the peptide. These results therefore establish how photosensitizer and peptide act in synergy to achieve bacterial photo-inactivation. Learning how to exploit and optimize this synergy should lead to the development of future bacterial photoinactivation agents that are effective at low concentrations and at low light doses.



Author: Johnson, Gregory A.; Ellis, E. Ann; Kim, Hansoo; Muthukrishnan, Nandhini; Snavely, Thomas; Pellois, Jean-Philippe

Source: https://archive.org/







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