title: Photodynamic inactivation of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with Ru(II)-based type I/type II photosensitizers.
abstract: BACKGROUND
  The introduction of new disinfection and sterilization methods, such as antimicrobial photodynamic therapy, is urgently needed for the healthcare industry, in particular to address the pervasive problem of antibiotic resistance. This study evaluated the efficacy and the mechanisms of photodynamic antimicrobial chemotherapy (PACT), also known as photodynamic inactivation (PDI) of microorganisms, induced by novel Ru(II)-based photosensitizers against Staphylococcus aureus and methicillin-resistant S. aureus strains.
  
  
  METHODS
  The photodynamic antibacterial effects of a new class of Ru(II)-based photosensitizers (TLD1411 and TLD1433) were evaluated against a strain of S. aureus (ATCC 25923) and a methicillin-resistant strain of S. aureus (MRSA, ATCC 33592). Bacterial samples were dosed with a range of photosensitizer concentrations (0.3-12 μM) and exposed to 530 nm light (90J cm(-2)) in normoxic conditions (ambient atmosphere) and in hypoxic conditions (0.5% O2).
  
  
  RESULTS
  Both photosensitizers exerted photodynamic inactivation (PDI) of the microorganisms in normoxia, and this activity was observed in the nanomolar regime. TLD1411 and TLD1433 maintained this PDI potency under hypoxic conditions, with TLD1433 becoming even more active in the low-oxygen environment.
  
  
  CONCLUSIONS
  The observation of activity in hypoxia suggests that there exists an oxygen-independent, Type I photoprocess for this new class of compounds in addition to the typical Type II pathway mediated by singlet oxygen. The intrinsic positive charge of the Ru(II) metal combined with the oxygen independent activity demonstrated by this class of photosensitizers presents a new strategy for eradicating both gram-positive and gram-negative bacteria regardless of oxygenation level.
authors.affiliation: Theralase Technologies, 1945 Queen St. East, Toronto, ON M4L 1H7, Canada. Electronic address: yarenas@theralase.com.
authors.forename: Yaxal
authors.initials: Y
authors.lastname: Arenas
authors.forename: Susan
authors.initials: S
authors.lastname: Monro
authors.forename: Ge
authors.initials: G
authors.lastname: Shi
authors.forename: Arkady
authors.initials: A
authors.lastname: Mandel
authors.forename: Sherri
authors.initials: S
authors.lastname: McFarland
authors.forename: Lothar
authors.initials: L
authors.lastname: Lilge
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D004203:Disinfection / Q000379:methods*; D016106:Methicillin Resistance / Q000187:drug effects* / Q000528:radiation effects*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D012428:Ruthenium / Q000008:administration & dosage*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects
chemical_list: D017319:Photosensitizing Agents; D012428:Ruthenium
keywords: Antibiotic-resistant bacteria; Methicillin-resistant Staphylococcus aureus; Nosocomial infection; Photodynamic antimicrobial chemotherapy (PACT); Photodynamic inactivation (PDI); Ru-based photosensitizers; Staphylococcus aureus; Sterilization