title: Stable synthetic mono-substituted cationic bacteriochlorins mediate selective broad-spectrum photoinactivation of drug-resistant pathogens at nanomolar concentrations.
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 24h 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/cm(2)). 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.
authors.affiliation: Department of Infectious Diseases, First Affiliated College & Hospital, Guangxi Medical University, Nanning 530021, China; Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, United States; Department of Dermatology, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Liyi
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Krayer
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, United States.
authors.forename: John G S
authors.initials: JG
authors.lastname: Roubil
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, United States; Department of Dermatology, Harvard Medical School, Boston, MA 02115, United States.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Huang
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, United States.
authors.forename: Dewey
authors.initials: D
authors.lastname: Holten
authors.affiliation: Department of Chemistry, North Carolina State University, Raleigh, NC 27695, United States.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Lindsey
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, United States; Department of Dermatology, Harvard Medical School, Boston, MA 02115, United States; Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, United States. Electronic address: hamblin@helix.mgh.harvard.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002176:Candida albicans / Q000187:drug effects / Q000528:radiation effects; D002412:Cations / Q000737:chemistry; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000528:radiation effects; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000528:radiation effects; D025141:Drug Resistance, Fungal / Q000187:drug effects* / Q000528:radiation effects; D005456:Fluorescent Dyes / Q000737:chemistry; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000528:radiation effects; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008027:Light; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002412:Cations; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin; D026082:Singlet Oxygen