Fungicidal Photodynamic Effect of a Twofold Positively Charged Porphyrin Against Candida Albicans Planktonic Cells and Biofilms

Abstract

Background: Antimicrobial photodynamic therapy is an interesting alternative for the treatment of superficial mucocutaneous mycoses. In immunodeficient patients, these infections are frequently recurrent and resistant to the most commonly used antifungal medications. Candida albicans biofilms frequently cause such infections that can even evolve to deep-seated mycoses. Materials & methods: The efficiency of a photodynamic therapy was investigated against C. albicans using a twofold positively charged porphyrin (XF-73) in comparison with the well-known fourfold positively charged porphyrin (5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H,23H-porphine, tetra-p-tosylate salt). Results: After incubation with 0.5 µM of XF-73 for 15 min and irradiation with blue light (12.1 J/cm2), the viability of C. albicans planktonic cells decreased by over 6 log10. For biofilm cells, a longer incubation time (4 h) with 1 µM of XF-73 and a light dose of 48.2 J/cm2 was necessary to achieve over 5 log10 cell killing. Cell killing was mediated by singlet oxygen that was directly detected via its luminescence at 1270 nm in XF-73-incubated C. albicans biofilms for the first time. Antimicrobial photodynamic therapy yielded better results for XF-73 compared with 5,10,15,20-tetrakis(1-methyl-4-pyridyl)-21H,23H-porphine, tetra-p-tosylate salt when using the same conditions. Conclusion: This study provides evidence that XF-73 is a highly efficient photosensitizer to kill C. albicans and it would be worthwhile to test this photosensitizer in clinical studies for both prophylaxis and treatment of infections caused by this microorganism, preventing the spread of C. albicans throughout the bloodstream.

Antibiotics in the clinical pipeline at the end of 2015

“…165 Exeporfinium chloride (27) is a photosensitizer that has broad-spectrum G+ve activity [166][167][168][169][170] and activity against Candida albicans. 171 Auriclosene (28) (NVC-422, N,N-dichloro-2,2-dimethyltaurine) is an N-dichlorotaurine analog being evaluated in phase-II trials by NovaBay Pharmaceuticals, Inc. (Emeryville, CA, USA) as an irrigation solution on urinary catheter patency (NCT02130518). It recently completed a phase-II trial for the treatment of bacterial conjunctivitis (NCT01877694).…”

Antimicrobial photodynamic therapy for inactivation of biofilms formed by oral key pathogens

“…With respect to porphyrins, TMPyP [5,10,15,20-tetrakis(1-methyl-4-pyridinium)-porphyrin tetra-(p-toluenesulfonate]—a fourfold positively charged derivative—has to be regarded as the most commonly used PS (Di Poto et al, 2009; Collins et al, 2010; Maisch et al, 2012; Cieplik et al, 2013b; Eichner et al, 2013; Gonzales et al, 2013). Di Poto et al (2009) cultured biofilms from three distinct strains of Staphylococcus aureus for 24 h, incubated them with TMPyP at a concentration of 10 μ M for 15 min and irradiated them with increasing doses of white light (150–200 J/cm 2 ) isolated from the emission of a tungsten lamp (166 mW/cm 2 ; 400–800 nm), whereby this treatment exhibited a rate of bacteria killing of 1 to 2 log 10 steps at the highest light dose depending on the strain, which was tested.…”

“…Pereira Gonzales et al (2013) compared the antimicrobial efficacy of XF-73 [5,15-bis-[4-(3-trimethylammoniopropyloxy)-phenyl]-porphyrin chloride]—a porphyrin derivative with two positive charges only—to that of TMPyP for inactivation of Candida albicans biofilms. These biofilms were cultured for 24 h, incubated with increasing concentrations of PS for 4 h and illuminated with an incoherent light source (13.4 mW/cm 2 ; 418 ± 20 nm) for 60 min, whereby a light dose of 48.2 J/cm 2 was applied.…”

“…Results showed CFU reductions of more than 5 log 10 for concentrations of 1.0 μ M of XF-73 at least, whereas for TMPyP concentrations of 50 μ M were needed at the minimum for obtaining equal antimicrobial results. This was explained due to stronger electrostatic interactions of TMPyP with the EPS compared to XF-73 leading to a lower degree of diffusion of the PS into the biofilm (Gonzales et al, 2013). …”

Topical Antimicrobials for Burn Infections – An Update

“…The reactive oxygen species produced by the photodynamic inactivation of these drugs possess antimicrobial traits and are effective against a broader spectrum of pathogens [234]. It has also been demonstrated that the compound exhibits fungicidal activity against C. albicans when used as a photosensitizer with blue light excitation [235]. …”