Carboranyl-Chlorin e6 as a Potent Antimicrobial Photosensitizer

PLoS One. 2015 Nov 4;10(11):e0141990. doi: 10.1371/journal.pone.0141990. eCollection 2015.

Abstract

Antimicrobial photodynamic inactivation is currently being widely considered as alternative to antibiotic chemotherapy of infective diseases, attracting much attention to design of novel effective photosensitizers. Carboranyl-chlorin-e6 (the conjugate of chlorin e6 with carborane), applied here for the first time for antimicrobial photodynamic inactivation, appeared to be much stronger than chlorin e6 against Gram-positive bacteria, such as Bacillus subtilis, Staphyllococcus aureus and Mycobacterium sp. Confocal fluorescence spectroscopy and membrane leakage experiments indicated that bacteria cell death upon photodynamic treatment with carboranyl-chlorin-e6 is caused by loss of cell membrane integrity. The enhanced photobactericidal activity was attributed to the increased accumulation of the conjugate by bacterial cells, as evaluated both by centrifugation and fluorescence correlation spectroscopy. Gram-negative bacteria were rather resistant to antimicrobial photodynamic inactivation mediated by carboranyl-chlorin-e6. Unlike chlorin e6, the conjugate showed higher (compared to the wild-type strain) dark toxicity with Escherichia coli ΔtolC mutant, deficient in TolC-requiring multidrug efflux transporters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Cell Membrane / metabolism*
  • Chlorophyllides
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Liposomes / metabolism
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Spectrometry, Fluorescence

Substances

  • Anti-Infective Agents
  • Bacterial Outer Membrane Proteins
  • Chlorophyllides
  • Escherichia coli Proteins
  • Liposomes
  • Membrane Transport Proteins
  • Photosensitizing Agents
  • Porphyrins
  • tolC protein, E coli
  • phytochlorin

Grants and funding

This work was financially supported by the Russian Science Foundation (No. 14-50-00029).