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Abstract
The emergence of antibiotic-resistant strains in facultative anaerobic Gram-positive coccal bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), is a global health issue. Typically, MRSA strains are found associated with institutions like hospitals but recent data suggest that they are becoming more prevalent in community-acquired infections. It is thought that the incidence and prevalence of bacterial infections will continue to increase as (a) more frequent use of broad-spectrum antibiotics and immunosuppressive medications; (b) increased number of invasive medical procedures; and (c) higher incidence of neutropenia and HIV infections. Therefore, more optimal treatments, such as photodynamic therapy (PDT), are warranted. PDT requires the interaction of light, a photosensitizing agent, and molecular oxygen to induce cytotoxic effects. In this study, we investigated the efficacy and characterized the mechanism of cytotoxicity induced by photodynamic therapy sensitized by silicon phthalocyanine (Pc) 4 on (a) methicillin-sensitive Staphylococcus aureus (MSSA) (ATCC 25923); (b) community acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) (ATCC 43300); and (c) hospital acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) (PFGE type 300). Our data include confocal image analysis, which confirmed that Pc 4 is taken up by all S. aureus strains, and viable cell recovery assay, which showed that concentrations as low as 1.0 μM Pc 4 incubated for 3 h at 37 °C followed by light at 2.0 J/cm2 can reduce cell survival by 2–5 logs. These results are encouraging, but before PDT can be utilized as an alternative treatment for eradicating resistant strains, we must first characterize the mechanism of cell death that Pc 4-based PDT employs in eliminating these pathogens.
Highlights
The rapid replication of bacteria in combination with the occurrence of mutations that improve bacterial survival in the presence of antibiotics results in highly resistant bacterial strains
To substantiate the photodynamic therapy (PDT) effect in S. aureus, we examined the uptake of phthalocyanine (Pc) 4 by confocal microscopy
CA-methicillin-resistant Staphylococcus aureus (MRSA)) was normalized against cultures exposed to Pc 4 or light alone (A); The three strains are significantly affected by one single dose of Pc 4-PDT (1.0 μM and 2.0 J/cm2)
Summary
The rapid replication of bacteria in combination with the occurrence of mutations that improve bacterial survival in the presence of antibiotics results in highly resistant bacterial strains. Staphylococcus aureus (MRSA) is the most common pathogen of hospital-associated infections in the United States [1]. In 2011, the Centers for Disease Control and Prevention (CDC) reported that MRSA caused 80,000 infections and more than 11,000 deaths in the United States alone [2]. The rise of community associated methicillin resistant Staphylcocus aureus (CA-MRSA). Photosensitizers are known to preferentially accumulate in cells that are actively dividing and pathogenic agents grow at much faster rate than the mammalian cells [17]. Photosensitizers are known to accumulate in normal healthy cells, the photodynamic effect can be targeted to unwanted cells by anatomically confining the delivery of the light source. The overall toxicity or adverse effects to the host can be reduced [18]
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