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

Liyi Huang, Michael Krayer, John G.S. Roubil, Ying Ying Huang, Dewey Holten, Jonathan S. Lindsey, Michael R. Hamblin

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)119-127
Number of pages9
JournalJournal of Photochemistry and Photobiology B: Biology
Volume141
DOIs
Publication statusPublished - Dec 2014
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology, Nuclear Medicine and Imaging

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