Abstract
Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 μg/ml) as a photosensitizing agent and light emitting diode (635 ± 10 nm, 12 and 24 J/cm2), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of ≥16, 4-8, 4-8, and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in SMIC50 and SMIC80 compared to untreated groups for both species, except SMIC80 of itraconazole against Fusarium biofilms. In conclusion, in vitro photodynamic therapy was efficient in inactivation of Fusarium spp. and Exophiala spp., both planktonic cultures and biofilms. In addition, the combination of aPDT and antifungal drugs represents an attractive alternative to the current antifungal strategies. However, further investigations are warranted for the reliable and safe application in clinical practice.
Highlights
Opportunistic fungi may causes cutaneous, subcutaneous and serious invasive infections, especially in immunocompromised and debilitated individuals
The antimicrobial photodynamic therapy (aPDT) with methylene blue and light emitting diode (LED) exhibited colony-forming unit (CFU) reductions of up to 3.8 log10 and 6.4 log10 against planktonic Exophiala spp. and Fusarium spp., respecitvely, and 4.2 log10 and 5.6 log10 against biofilms formed by Exophiala spp. and Fusarium spp., respecitvely, demonstrating efficacy in reducing the growth of both planktonic cultures and biofilms in all concentrations of methylene blue (Table 1 and Figures 1A–D)
A variety of PSs have been used in antifungal photodynamic inactivation, including toluidine blue, methylene blue, Rose Bengal, porphyrins, phthalocyanines, 5-aminolevulinic acid, and curcumin (Calzavara-Pinton et al, 2012; Baltazar et al, 2015)
Summary
Opportunistic fungi may causes cutaneous, subcutaneous and serious invasive infections, especially in immunocompromised and debilitated individuals. Human infection usually occurs as a result of inoculation of the organism through the body surface causing local infection. Systemic dissemination, whose prevalence is effectively growing, occurs in subjects with underlying immunodeficiency (Li et al, 2011; Guarro, 2013), which is often refractory to available antifungal therapies and thereby leads to death (Filizzola et al, 2003; Guarro, 2013). Available antifungal drugs have shown poor in vitro activity against Fusarium spp. As for Exophiala spp. infection, success rate was only 40–70% favorable in vitro activity of most antifungal drugs has been shown (Revankar and Sutton, 2010; Kondori et al, 2011; Patel et al, 2013). In addition to life-threatening infection, more frequently they result in significant morbidity, causing discomfort, disfigurement, social isolation, and they are usually recurrent and chronic
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