Photodynamic Inactivation of the Dermatophyte Trichophyton rubrum¶

Photodynamic therapy is a rapidly developing antimicrobial technology which combines a nontoxic photoactivatable dye or photosensitizer with harmless visible light of the correct wavelength to excite the dye to its reactive triplet state to generate reactive oxygen species toxic to cells. In this report we present evidence that the fungal pathogen Cryptococcus neoformans is susceptible to photodynamic inactivation by use of a polycationic conjugate of polyethyleneimine and the photosensitizer chlorin(e6). A C. neoformans rom2 mutant, with a mutation involving a putative Rho1 guanyl nucleotide exchange factor that is part of the protein kinase C-cell wall integrity pathway, demonstrated a compromised cell wall and less (1,3)␤-D glucan than the wild-type strain and increased accumulation of PEI-ce6 as assessed by fluorescence uptake and confocal microscopy. Interestingly, C. neoformans rom2 was hypersusceptible to photodynamic inactivation and coincubation of wild-type C. neoformans strain KN99␣ with caspofungin-enhanced photoinactivation. These studies demonstrated that C. neoformans is sensitive to photodynamic therapy and illustrated the significance of cell wall integrity in microbial susceptibility to antimicrobial photodynamic inactivation.

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“…Growth inhibition was achieved with thiophenes 2. (41). Our findings show that PEI-ce6 can be used for photoinactivation of C. neoformans.…”

Section: Resultsmentioning

confidence: 66%

Susceptibility of Cryptococcus neoformans to Photodynamic Inactivation Is Associated with Cell Wall Integrity

Fuchs

Tegos

Hamblin

et al. 2007

Antimicrob Agents Chemother

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“…Pc 4-PDT also demonstrated an excellent safety profile in a phase 1 trial on cutaneous neoplasms (25). Although the susceptibility of T. rubrum to PDT using other photosensitizers has been extensively investigated in vitro, the mechanism of phototoxicity has not been clearly defined (2,9,(26)(27)(28). In this study, we showed that a common dose of Pc 4-PDT can induce cell death in microconidia (terbinafine-sensitive and -resistant strains of T. rubrum).…”

mentioning

confidence: 78%

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

Lam

Dimaano

Oyetakin-White

et al. 2014

Antimicrob Agents Chemother

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dTrichophyton rubrum is the leading pathogen that causes long-lasting skin and nail dermatophyte infections. Currently, topical treatment consists of terbinafine for the skin and ciclopirox for the nails, whereas systemic agents, such as oral terbinafine and itraconazole, are also prescribed. These systemic drugs have severe side effects, including liver toxicity. Topical therapies, however, are sometimes ineffective. This led us to investigate alternative treatment options, such as photodynamic therapy (PDT). Although PDT is traditionally recognized as a therapeutic option for treating a wide range of medical conditions, including agerelated macular degeneration and malignant cancers, its antimicrobial properties have also received considerable attention. However, the mechanism(s) underlying the susceptibility of dermatophytic fungi to PDT is relatively unknown. As a noninvasive treatment, PDT uses a photosensitizing drug and light, which, in the presence of oxygen, results in cellular destruction. In this study, we investigated the mechanism of cytotoxicity of PDT in vitro using the silicon phthalocyanine (Pc) 4 [SiPc(OSi(CH 3 ) 2 (CH 2 ) 3 N(CH 3 ) 2 )(OH)] in T. rubrum. Confocal microscopy revealed that Pc 4 binds to cytoplasmic organelles, and upon irradiation, reactive oxygen species (ROS) are generated. The impairment of fungal metabolic activities as measured by an XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay indicated that 1.0 M Pc 4 followed by 670 to 675 nm light at 2.0 J/cm 2 reduced the overall cell survival rate, which was substantiated by a dry weight assay. In addition, we found that this therapeutic approach is effective against terbinafine-sensitive (24602) and terbinafine-resistant (MRL666) strains. These data suggest that Pc 4-PDT may have utility as a treatment for dermatophytosis. Utilizing mainly keratin for their source of energy, dermatophytes can cause dermatophytosis or tinea of the skin, hair, and nails that impact the quality of life of infected patients, especially in immunocompromised individuals. Trichophyton rubrum is the main culprit of superficial mycosis of the nail (onychomycosis), which is often long lasting and has a high incidence of recurrence. Onychomycosis affects 10% of the general population, 20% of the population older than 60 years, 50% of people older than 70 years, and 30% of diabetic patients, and it can often result in pain, disability, and psychosocial stress, therefore significantly reducing quality of life (1-3). The conventional treatments involve excruciating surgical nail avulsion and toxic systemic antifungal drugs. Topical therapy is a less invasive and hence more attractive treatment for the eradication of fungal infection. However, dismal patient compliance often contributes to the high rate of unsuccessful treatment (4). It is for these reasons that alternative therapeutic agents need to be developed that can effectively target T. rubrum without significantly harming the host.In vitro studies have dem...

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“…Recently, the antimicrobial efficacy of PDT with endogenous porphyrins was highlighted in reports that found it to be effective against bacteria, virus, fungi, and protozoa [5,[12][13][14][15][16][17]. Thus, in this study, we attempted to treat recalcitrant Malassezia folliculitis with MAL-PDT.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy: New treatment for recalcitrant Malassezia folliculitis

Lee

Kim

2010

Lasers Surg Med

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BackgroundMalassezia folliculitis commonly has been treated with oral antifungal medications. However, it has many therapeutic weaknesses such as infection relapse, drug resistance, or adverse effects like hepatotoxicity and gastrointestinal discomfort. Hence, there remains an ongoing need for alternative treatments for recalcitrant Malassezia folliculitis. Recently, many dermatologists suggest photodynamic therapy (PDT) as an alternative therapeutic option for its antimicrobial effect.ObjectiveTo investigate the efficacy of methyl 5‐aminolevulinic acid (MAL)‐PDT for the treatment of recalcitrant Malassezia folliculitis.Materials and MethodsSix Korean patients aged 23–47 years with recalcitrant Malassezia folliculitis were enrolled in this study. The patients enrolled in this study either refused oral medication or were unable to take oral antifungal agents due to hepatotoxicity concerns. Thus, we offered these patients MAL‐PDT as an alternative treatment option. For all patients, photographs of the lesion(s) were taken prior to initiating treatment. MAL cream (Metvix®, Galderma, France) was applied to each lesion (located on the patients' trunks) and covered with an adhesive occlusive dressing polyurethane film (Tegaderm®, 3M Healthcare, St. Paul, MN). After 3 hours, the cream was wiped off and illumination was performed immediately thereafter with non‐coherent red light using light‐emitting diodes (Aktilite® lamp, PhotoCure, Oslo, Norway, average wavelength 630 nm, light dose 37 J/cm2). Illumination was performed for 7.5 minutes. Patients underwent totally three sessions of MAL‐PDT at 2‐week intervals. One month after the last PDT treatment, patients returned to the hospital and lesions were photographed.ResultsAfter three sessions of MAL‐PDT, inflammatory lesions had decreased and improved obviously in four patients, had improved slightly in one patient, and had not improved in one patient.ConclusionMAL‐PDT may be an effective treatment option for patients with recalcitrant Malassezia folliculitis. However, the data on MAL‐PDT are still limited, and additional controlled trials including multiple patients will be necessary to verify the results of this pilot study. Lasers Surg. Med. 42:192–196, 2010. © 2010 Wiley‐Liss, Inc.

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Photodynamic Inactivation of the Dermatophyte Trichophyton rubrum¶

Cited by 28 publications

References 11 publications

Susceptibility of Cryptococcus neoformans to Photodynamic Inactivation Is Associated with Cell Wall Integrity

Susceptibility of Cryptococcus neoformans to Photodynamic Inactivation Is Associated with Cell Wall Integrity

Silicon Phthalocyanine 4 Phototoxicity in Trichophyton rubrum

Photodynamic therapy: New treatment for recalcitrant Malassezia folliculitis

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