Resistance of melanized yeast cells of Paracoccidioides brasiliensis to antimicrobial oxidants and inhibition of phagocytosis using carbohydrates and monoclonal antibody to CD18

Silva, Marcelo Barbosa da; Thomaz, Luciana Costa Lima; Marques, Alexandre F.; Svidzinski, Artur E.; Nosanchuk, J. D.; Casadevall, Arturo; Travassos, Luiz R.; Taborda, Carlos Pelleschi

doi:10.1590/s0074-02762009000400019

Cited by 30 publications

(25 citation statements)

References 33 publications

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“…The variation of the area may be related to the Pb virulence. The decrease in the amino acid content in the first week, compared to the control tissue, may be related to the use of tyrosine by Pb to synthesize melanin, a mechanism that increases its resistance to antifungal activities of macrophages [54]–[56] making it more resistant to the host immune system. The increase in the area after the second week of infection indicates the occurrence of a reaction of the body against Pb.…”

Section: Discussionmentioning

confidence: 99%

Correlation between Histopathological and FT-Raman Spectroscopy Analysis of the Liver of Swiss Mice Infected with Paracoccidioides brasiliensis

et al. 2014

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Paracoccidioidomycosis is the most important systemic mycosis in Latin America. The main entrance of the fungus is the airway. It primarily occurs in the lung, but in its disseminated form may affect any organ. The liver is one of the organs afflicted by this disease and its homeostasis may be impaired. The aim of the present study was to evaluate the evolution of paracoccidioidomycosis in the liver of Swiss mice and correlate morphological factors with the expression of gp43 and with physicochemical analysis via FT-Raman of the infected organ. According to colony forming unit (CFU) and granuloma counting, the first and second weeks were the periods when infection was most severe. Tissue response was characterized by the development of organized granulomas and widespread infection, with yeasts located within the macrophages and isolated hepatocytes. The gp43 molecule was distributed throughout the hepatic parenchyma, and immunostaining was constant in all observed periods. The main physicochemical changes of the infected liver were observed in the spectral ranges between 1700–1530 cm−1 and 1370 – 1290 cm−1, a peak shifting center attributed to phenylalanine and area variation of -CH2 and -CH3 compounds associated to collagen, respectively. Over time, there was a direct proportional relationship between the number of CFUs, the number of granulomas and the physicochemical changes in the liver of mice infected with Paracoccidioides brasiliensis. The expression of gp43 was similar in all observed periods.

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Section: Discussionmentioning

confidence: 99%

Correlation between Histopathological and FT-Raman Spectroscopy Analysis of the Liver of Swiss Mice Infected with Paracoccidioides brasiliensis

et al. 2014

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“…In Cryptococcus gattii , a related organism and causative agent of the current cryptococcosis outbreak in Vancouver, analysis of more virulent and less virulent strains shows that the more virulent strains have greater expression of melanin synthesis genes and produce more melanin (Ngamskulrungroj et al 2011). Similarly, in Paracoccidioides brasiliensis , experimental infections with melanized cells result in higher fungal burdens in animals compared to nonmelanized cells (Silva et al 2009). In addition, infection increases the expression of melanin synthesis genes in this fungus (Bailao et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and assembly of fungal melanin

Eisenman

Casadevall

2011

Appl Microbiol Biotechnol

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591

463

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Melanin is a unique pigment with myriad functions that is found in all biological kingdoms. It is multifunctional, providing defense against environmental stresses such as ultraviolet (UV) light, oxidizing agents and ionizing radiation. Melanin contributes to the ability of fungi to survive in harsh environments. In addition, it plays a role in fungal pathogenesis. Melanin is an amorphous polymer that is produced by one of two synthetic pathways. Fungi may synthesize melanin from endogenous substrate via a 1,8-dihydroxynaphthalene (DHN) intermediate. Alternatively, some fungi produce melanin from l-3,4-dihydroxyphenylalanine (l-dopa). The detailed chemical structure of melanin is not known. However, microscopic studies show that it has an overall granular structure. In fungi, melanin granules are localized to the cell wall where they are likely cross-linked to polysaccharides. Recent studies suggest the fungal melanin may be synthesized in internal vesicles akin to mammalian melanosomes and transported to the cell wall. Potential applications of melanin take advantage of melanin's radioprotective properties and propensity to bind to a variety of substances.

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“…Currently, there has been much discussion about the role of melanin as a putative virulence factor of several fungal species, such as Histoplasma capsulatum, Sporothrix schenckii, and Cryptococcus neoformans (8)(9)(10)(11). Melanin is a multifunctional polymer synthesized from 1,8-dihydroxynaphthalene (DHN) by the pentakide pathway or formed when cells grow in the presence of phenolic compounds, such as L-3,4-dihydroxyphenylalanine (L-DOPA) (12).…”

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confidence: 99%

Melanin Protects Paracoccidioides brasiliensis from the Effects of Antimicrobial Photodynamic Inhibition and Antifungal Drugs

Baltazar

Werneck

Soares

et al. 2015

Antimicrob Agents Chemother

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c 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 Paracoccidioides 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 Paracoccidioides 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. P aracoccidioidomycosis (PCM) is a systemic disease endemic to Latin America and South America that can be fatal if not treated (1). In Brazil, PCM is a serious health problem and is the most important cause of death among the systemic mycoses in immunocompetent patients (1-3). The etiological agents of PCM, dimorphic fungi that present a filamentous form at 25°C and yeast forms at 37°C, belong to the Paracoccidioides species complex, which includes four known phylogenetic lineages, Pb01-like (or Paracoccidioides lutzii), S1, PS2, and PS3 (Paracoccidioides brasiliensis) (4-7). Thermal dimorphism is a survival strategy to resist the host environment (5, 7). It includes secretion of proteases and melanin synthesis as putative virulence factors contributing to the protection of yeast cells from environmental stressors (8).Currently, there has been much discussion about the role of melanin as a putative virulence factor of several fungal species, such as Histoplasma capsulatum, Sporothrix schenckii, and Cryptococcus neoformans (8-11). Melanin is a multifunctional polymer synthesized from 1,8-dihydroxynaphthalene (DHN) by the pentakide pathway or formed when cells grow in the presence of phenolic compounds, such as L-3,4-dihydroxyphenylalanine (L-DOPA) (12). Typically, it is a brown to black pigment formed through the activity of the phenoloxidase enzyme (laccase) on phenolic compounds (8, 13). Its influence on the biology of fungal cells is better ...

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Resistance of melanized yeast cells of Paracoccidioides brasiliensis to antimicrobial oxidants and inhibition of phagocytosis using carbohydrates and monoclonal antibody to CD18

Cited by 30 publications

References 33 publications

Correlation between Histopathological and FT-Raman Spectroscopy Analysis of the Liver of Swiss Mice Infected with Paracoccidioides brasiliensis

Correlation between Histopathological and FT-Raman Spectroscopy Analysis of the Liver of Swiss Mice Infected with Paracoccidioides brasiliensis

Synthesis and assembly of fungal melanin

Melanin Protects Paracoccidioides brasiliensis from the Effects of Antimicrobial Photodynamic Inhibition and Antifungal Drugs

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