title: Photodynamic inactivation of Paracoccidioides brasiliensis helps the outcome of oral paracoccidiodomycosis.
abstract: The antifungal drug therapy often employed to treat paracoccidiodomycosis (PCM), an important neglected fungal systemic infection, leads to offensive adverse effects, besides being very long-lasting. In addition, PCM compromises the oral health of patients by leading to oral lesions that are very painful and disabling. In that way, photodynamic therapy (PDT) arises as a new promising adjuvant treatment for inactivating Paracoccidioides brasiliensis (Pb), the responsible fungus for PCM, and also for helping the patients to deal with such debilitating oral lesions. PDT has been linked to an improved microbial killing, also presenting the advantage of not inducing immediate microbial resistance such as drugs. For the present study, we investigated the generation of reactive oxygen species (ROS) by using the fluorescent probes hydroxyphenyl fluorescein (HPF) and aminophenyl fluorescein (APF) after toluidine blue (TBO-37.5 mg/L)-mediated PDT (660 nm, 40 mW, and 0.04 cm2spot area) and the action of TBO-PDT upon Pb cultures grown for 7 or 15 days in semisolid Fava Netto's culture medium; we also targeted oral PCM manifestations by reporting the first clinical cases (three patients) to receive topic PDT for such purpose. We were able to show a significant generation of hydroxyl radicals and hypochlorite after TBO-PDT with doses around 90 J/cm2; such ROS generation was particularly useful to attack and inactivate Pb colonies at 7 and 15 days. All three patients reported herein related an immediate relief when it came to pain, mouth opening, and also the ability to chew and swallow. As extracted from our clinical results, which are in fact based on in vitro outcomes, TBO-PDT is a very safe, inexpensive, and promising therapy for the oral manifestations of PCM.
authors.affiliation: School of Dentistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Letícia F M
authors.initials: LFM
authors.lastname: Dos Santos
authors.affiliation: School of Dentistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Nathália B
authors.initials: NB
authors.lastname: Melo
authors.affiliation: Department of Clinics and Surgery, School of Dentistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Marina L
authors.initials: ML
authors.lastname: de Carli
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Ana Carolina S C
authors.initials: ACSC
authors.lastname: Mendes
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Giulia Maria A C
authors.initials: GMAC
authors.lastname: Bani
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, 13083-865, Brazil.
authors.forename: Liana M
authors.initials: LM
authors.lastname: Verinaud
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Eva
authors.initials: E
authors.lastname: Burger
authors.affiliation: Department of Biochemistry, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: de Oliveira I Moraes
authors.affiliation: Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, Brazil.
authors.forename: Alessandro A C
authors.initials: AAC
authors.lastname: Pereira
authors.affiliation: Department of Biochemistry, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: Maísa R L
authors.initials: MRL
authors.lastname: Brigagão
authors.affiliation: Department of Clinics and Surgery, School of Dentistry, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-000, Brazil.
authors.forename: João Adolfo C
authors.initials: JAC
authors.lastname: Hanemann
authors.affiliation: Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, Brazil. sperandio@usp.br.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Sperandio
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008297:Male; D050296:Microbial Viability / Q000187:drug effects*; D008875:Middle Aged; D009059:Mouth Diseases / Q000188:drug therapy* / Q000382:microbiology* / Q000473:pathology; D010228:Paracoccidioides / Q000254:growth & development / Q000528:radiation effects*; D010229:Paracoccidioidomycosis / Q000188:drug therapy* / Q000382:microbiology*; D010778:Photochemotherapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D014048:Tolonium Chloride / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D014048:Tolonium Chloride
keywords: Paracoccidioides; Paracoccidioidomycosis; Photodynamic therapy; Reactive oxygen species; Toluidine blue