title: Susceptibility of methicillin-resistant Staphylococcus aureus to photodynamic antimicrobial chemotherapy with α-D-galactopyranosyl zinc phthalocyanines: in vitro study.
abstract: The incidence of methicillin-resistant strains of Staphylococcus aureus (MRSA) is increasing globally, making urgent the discovery of novel alternative therapies for infections. Photodynamic antimicrobial chemotherapy (PACT), based on oxidative damage to subcellular structures, has the advantage of circumventing multidrug resistance, and is becoming a potential therapeutic modality for methicillin-resistant bacteria. The key to PACT is photosensitization. This study demonstrates the efficiency of PACT using α-D-galactopyranosyl zinc phthalocyanines (T1-T4) for the photosensitization of MRSA, Escherichia coli, and Pseudomonas aeruginosa. Bacterial suspensions were illuminated with 650-nm light from a semiconductor laser at 0.2 W/cm(2), and the energy density was maintained at 6 J/cm(2) in the presence of different concentrations of photosensitizer. The treatment response was evaluated based on the numbers of bacterial colony-forming units. PACT with these phthalocyanines strongly affected MRSA, but weakly affected E. coli and P. aeruginosa. The efficiency of PACT on MRSA with these four phthalocyanine compounds decreased in the order T1 > T2 > T3 > T4. T1-PACT eliminated >99% of MRSA in a concentration range of 25-50 μM and at an energy density of 6 J/cm(2). Uptake measurements revealed that the PACT effect correlated with the bacterial uptake of the photosensitizer and that 4-30-fold more T1 than T2-T4 was taken up by the MRSA strain, which was confirmed with laser confocal microscopy. These data suggest that T1 is an efficient PACT photosensitizer for MRSA.
authors.affiliation: Institute of Biomedical Engineering, Tianjin Key Laboratory of Biomedical Material, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, People's Republic of China.
authors.forename: Zhanjuan
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Meng
authors.forename: Shaozeng
authors.initials: S
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Tianjun
authors.initials: T
authors.lastname: Liu
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D005690:Galactose / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D017967:Zinc Compounds
chemical_list: D000890:Anti-Infective Agents; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine; D005690:Galactose