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Stable synthetic mono-substituted cationic bacteriochlorins mediate selective broad-spectrum photoinactivation of drug-resistant pathogens at nanomolar concentrations

Paper ID Volume ID Publish Year Pages File Format Full-Text
29846 44444 2014 9 PDF Available
Title
Stable synthetic mono-substituted cationic bacteriochlorins mediate selective broad-spectrum photoinactivation of drug-resistant pathogens at nanomolar concentrations
Abstract

•Stable synthetic monosubstituted cationic bacteriochlorins for antimicrobial photoinactivation.•Broad-spectrum killing of 6 logs of Gram-positive bacteria, Gram-negative bacteria and fungi.•Activated with near-infrared light and highly active at nanomolar concentration.•No killing of mammalian cells under the same conditions with a short incubation time.•Mechanism of action is primarily via singlet oxygen but hydroxyl radicals may also be involved.

Three stable synthetic mono-substituted cationic bacteriochlorins (BC37, BC38 and BC39) were recently reported to show exceptional activity (low nanomolar) in mediating photodynamic killing of human cancer cells after a 24 h incubation upon excitation with near-infrared light (730 nm). The presence of cationic quaternary ammonium groups in each compound suggested likely activity as antimicrobial photosensitizers. Herein this hypothesis was tested against a panel of pathogenic microorganisms that have all recently drawn attention due to increased drug-resistance (Gram-positive bacteria, Staphylococcus aureus and Enterococcus faecalis; Gram-negative bacteria, Escherichia coli and Acinetobacter baumannii; and fungal yeasts, Candida albicans and Cryptococcus neoformans). All three bacteriochlorins were highly effective against both Gram-positive species (>6 logs of eradication at ⩽200 nM and 10 J/cm2). The dicationic bacteriochlorin (BC38) was best against the Gram-negative species (>6 logs at 1–2 μM) whereas the lipophilic monocationic bacteriochlorin (BC39) was best against the fungi (>6 logs at 1 μM). The bacteriochlorins produced substantial singlet oxygen (and apparently less Type-1 reactive-oxygen species such as hydroxyl radical) as judged by activation of fluorescent probes and comparison with 1H-phenalen-1-one-2-sulfonic acid; the order of activity was BC37 > BC38 > BC39. A short incubation time (30 min) resulted in selectivity for microbial cells over HeLa human cells. The highly active photodynamic inactivation of microbial cells may stem from the amphiphilic and cationic features of the bacteriochlorins.

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Stable synthetic mono-substituted cationic bacteriochlorins mediate selective broad-spectrum photoinactivation of drug-resistant pathogens at nanomolar concentrations
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 141, December 2014, Pages 119–127
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
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