Approaches to selectivity in the Zn(ii)–phthalocyanine-photosensitized inactivation of wild-type and antibiotic-resistant Staphylococcus aureus

Abstract

A number of Zn(II)- phthalocyanines bearing peripheral substituents of cationic nature due to the presence of quaternarized anilinium or ammonium groups were shown to be efficient photoantimicrobial agents: a 4-5 log decrease in the survival of both wild-type or methicillin-resistant Staphylococcus aureus was obtained upon short irradiation times in the presence of phthalocyanine concentrations as low as 0.1 microM. A careful selection of the experimental protocol, and in particular the use of short (5 min) incubation times and mild irradiation parameters, allowed one to achieve a high selectivity of S. aureus photoinactivation as compared with important constituents of potential host tissues, such as human fibroblasts and keratinocytes. The efficiency and selectivity of the photoprocess were not affected by the presence of 5% human serum.

Photodynamic antimicrobial therapy

“…There is a permeable outer peptidoglycan layer in Gram-positive bacteria, which enables the penetration of photosensitive substance to the cytoplasmatic membrane, the target of PACT. Thickening of the cell wall of MRSA (methicilin-resistant Staphylococcus aureus) or VRE (vancomycin-resistant enterococci) diminishes the penetration of antibiotics, antiseptics and disinfectants, however, the decrease in effectiveness of PACT has not been proved so far [18]. The wall of Gram- negative bacteria is more complex.…”

Mechanistic Study of the Photodynamic Inactivation of Candida albicans by a Cationic Porphyrin

“…In the last decade, cationic porphyrins (2,23,24), phthalocyanines (26,27,37), and chlorins (12) have gained popularity as antimicrobial photosensitizers due to their abilities to inactivate both gram-positive and gram-negative bacteria. This has fueled the thought that these photosensitizers could be successfully applied as broadband antimicrobial agents.…”

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…ZnPc predominantly gener- [54]. Native ZnPc was found to be ineffective against Gramnegative bacteria such as E.coli [48] and had to be applied in combination with membrane perturbing agents such as ethylenediaminetetraacetic acid (EDTA) or calcium chloride to ensure (intra)cellular delivery [23,55,56]. In contrast, ZnPc exhibited affinity for the Gram-positive Streptococcus mitis, which involved the association with membrane proteins residing in the cytoplasmic membrane [49,54].…”

“…Furthermore, the tertiary ammonium-substituted methylene blue derivative possesses lower pK a values than the lower-order substituents, which results in faster deprotonation when bound to the negatively charged bacterial cell envelope structure and better uptake. It was further shown that, by employing relatively short drug-light intervals, APDT of the infected area killed the photosensitized bacteria without damaging the surrounding healthy cells/tissues [22][23][24]. Phenothiazinium is also a substrate for multidrug resistance pumps [25,26], a family of transmembrane proteins that mediate the efflux of amphipathic cations, amongst others.…”