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Melanin Protects Paracoccidioides brasiliensis from the Effects of Antimicrobial Photodynamic Inhibition and Antifungal Drugs
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by
Ludmila Matos Baltazar,
Silvia Maria Cordeiro Werneck,
Betânia Maria Soares,
Marcus Vinicius L. Ferreira,
Danielle G. Souza,
Marcos Pinotti,
Daniel Assis Santos,
Patrícia Silva Cisalpino
Published
in Antimicrobial Agents and Chemotherapy
by American Society for Microbiology.
2015 Volume 59, p4003-4011
Abstract
<jats:title>ABSTRACT</jats:title>Paracoccidioidomycosis (PCM) is a public health concern in Latin America and South America that when not correctly treated can lead to patient death. In this study, the influence of melanin produced by<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Paracoccidioides</jats:named-content>spp. on the effects of treatment with antimicrobial photodynamic inhibition (aPI) and antifungal drugs was evaluated. aPI was performed using toluidine blue (TBO) as a photosensitizer and a 630-nm light-emitting diode (LED) light. The antifungals tested were itraconazole and amphotericin B. We evaluated the effects of each approach, aPI or antifungals, against nonmelanized and melanized yeast cells by performing susceptibility tests and by quantifying oxidative and nitrosative bursts during the experiments. aPI reduced nonmelanized cells by 3.0 log units and melanized cells by 1.3 log units. The results showed that melanization protects the fungal cell, probably by acting as a scavenger of nitric oxide and reactive oxygen species, but not of peroxynitrite. Melanin also increased the MICs of itraconazole and amphotericin B, and the drugs were fungicidal for nonmelanized and fungistatic for melanized yeast cells. Our study shows that melanin production by<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Paracoccidioides</jats:named-content>yeast cells serves a protective function during aPI and treatment with itraconazole and amphotericin B. The results suggest that melanin binds to the drugs, changing their antifungal activities, and also acts as a scavenger of reactive oxygen species and nitric oxide, but not of peroxynitrite, indicating that peroxynitrite is the main radical that is responsible for fungal death after aPI.
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