<i>Candida Glabrata</i>
            Produces a Melanin-Like Pigment that Protects Against Stress Conditions Encountered During Parasitism

Almeida‐Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Silva, Leandro Br da; Gerfen, Gary J.; Araújo, Glaucy Rodrigues de; Frasés, Susana; Zancopé‐Oliveira, Rosely Maria; Nosanchuk, Joshua D.

doi:10.2217/fmb-2020-0228

Cited by 9 publications

(10 citation statements)

References 33 publications

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“…Unlike C. neoformans melanin particles, which retain cellular shape and size after hot-acid treatment ( Wang et al, 1996 ), melanin from Trichosporonaceae species are smaller than original cells and tend to clump. Similar behavior was observed for other fungi, such as Candida albicans ( Morris-Jones et al, 2005 ) and Candida glabrata ( Almeida-Paes et al, 2021 ). These particles have shape and sizes that resemble fungal melanosomes, such as those observed in Fonsecaea pedrosoi ( Alviano et al, 1991 ).…”

Section: Discussionsupporting

confidence: 76%

Comparative Biophysical and Ultrastructural Analysis of Melanins Produced by Clinical Strains of Different Species From the Trichosporonaceae Family

et al. 2022

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Melanin is one of the most studied virulence factors in pathogenic fungi. This pigment protects them from a series of both environmental and host stressors. Among basidiomycetes, Cryptococcus neoformans and Trichosporon asahii are known to produce melanin in the presence of phenolic precursors. Other species from the Trichosporonaceae family also produce this pigment, but the extent to this production among the clinically relevant species is unknown. For this reason, the aim of this study was to verify the production of melanin by different Trichosporonaceae species of clinical interest and to compare their pigments with the ones from C. neoformans and T. asahii, which are more prevalent in human infections. Melanin was produced in a minimal medium supplemented with 1 mM L-dihydroxyphenylalanine (L-DOPA). Pigment was evaluated using scanning electron microscopy, Zeta potential measurements, and energy-dispersive X-ray spectroscopy. It was found that, besides C. neoformans and T. asahii, Trichosporon japonicum, Apiotrichum montevideense, Trichosporon inkin, Trichosporon faecale, Cutaneotrichosporon debeurmannianum, and Cutaneotrichosporon arboriformis also produce melanin-like particles in the presence of L-DOPA. Melanin particles have negative charge and are smaller than original cells. Variations in color, fluorescence, and chemical composition was noticed between the studied strains. All melanins presented carbon, oxygen, sodium, and potassium in their composition. Melanins from the most pathogenic species also presented iron, zinc, and copper, which are important during parasitism. Biophysical properties of these melanins can confer to the Trichosporonaceae adaptive advantages to both parasitic and environmental conditions of fungal growth.

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Section: Discussionsupporting

confidence: 76%

Comparative Biophysical and Ultrastructural Analysis of Melanins Produced by Clinical Strains of Different Species From the Trichosporonaceae Family

et al. 2022

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“…One unexplored aspect of C. auris physiology is whether it can produce the virulence factor melanin. Other Candida species, such as C. albicans and C. glabrata, produce this virulence factor [ 8 , 9 , 10 , 11 ]. Melanin is a black-brown, insoluble, acid-resistant pigment found throughout a plethora of life forms, and it has particular importance in the context of fungal virulence in mammals [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Melanization of Candida auris Is Associated with Alteration of Extracellular pH

Smith

Mudrak

Zamith-Miranda

et al. 2022

JoF

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Candida auris is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. C. auris infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, C. auris forms durable and difficult to remove biofilms. Due to the relatively recent, resilient, and resistant nature of C. auris, we investigated whether it produces the common fungal virulence factor melanin. Melanin is a black-brown pigment typically produced following enzymatic oxidation of aromatic precursors, which promotes fungal virulence through oxidative stress resistance, mammalian immune response evasion, and antifungal peptide and pharmaceutical inactivation. We found that certain strains of C. auris oxidized L-DOPA and catecholamines into melanin. Melanization occurred extracellularly in a process mediated by alkalinization of the extracellular environment, resulting in granule-like structures that adhere to the fungus’ external surface. C. auris had relatively high cell surface hydrophobicity, but there was no correlation between hydrophobicity and melanization. Melanin protected the fungus from oxidative damage, but we did not observe a protective role during infection of macrophages or Galleria mellonella larvae. In summary, C. auris alkalinizes the extracellular medium, which promotes the non-enzymatic oxidation of L-DOPA to melanin that attaches to its surface, thus illustrating a novel mechanism for fungal melanization.

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“…The EPR spectra of the collected dark particles were registered using a Varian E112 X-Band model spectrometer with a TE102 resonator and a liquid nitrogen finger Dewar. The EPR runs were performed under the following parameters that are similar to our fungal melanin studies as previously described (8): modulation frequency of 100 kHz, modulation amplitude of 1.6 G, center field of 3,310 G, sweep width of 100.0 G, microwave frequency of 9.2 GHz, microwave power of 1.0 mW, time constant of 0.5 s, and temperature of 77 K.…”

Section: Methodsmentioning

confidence: 99%

“…Extracted melanin was examined using a Varian E112 X-Band model spectrometer with a TE102 resonator and a liquid nitrogen finger Dewar vessel to obtain EPR spectra of the collected dark particles suspended in PBS and frozen with liquid nitrogen. The EPR runs were performed with the following parameters that were standardized for our fungal melanin studies as described previously (8): modulation frequency of 9.07 GHz, modulation amplitude of 1.6 G, center field of 3,250.0 G, sweep width of 100.0 G, microwave frequency of 9.1 GHz, microwave power of 1.0 mW, time constant of 0.5 s, and temperature of 77 K .…”

Section: Melanin Extraction and Electron Paramagnetic Resonance (Epr)mentioning

confidence: 99%

“…One unexplored aspect of C. auris physiology is whether it can produce the virulence factor melanin. Other Candida species, such as C. albicans and C. glabrata, produce this virulence factor (8)(9)(10)(11). Melanin is a black-brown, insoluble, acid resistant pigment found throughout a plethora of life forms, and it has particular importance in the context of fungal virulence in mammals (12,13).…”

Section: Introductionmentioning

confidence: 99%

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Melanization ofCandida aurisis Associated with Alteration of Extracellular pH

Smith

Mudrak

Zamith-Miranda

et al. 2022

Preprint

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Candida auris is a recently emerged global fungal pathogen, which causes life threatening infections, often in healthcare settings and with immunocompromised patients. C. auris infections are particularly worrisome because the fungus is often resistant to multiple classes of antifungal drugs. Furthermore, the fungus forms durable biofilms that are difficult to remove from surfaces. Due to the relatively recent, resilient, and resistant nature of this fungal pathogen, we investigated whether C. auris made common fungal virulence factor melanin. Melanin is a black-brown pigment that enables microbes to evade the mammalian immune response due to its strong antioxidant properties, ability to inactivate antimicrobial peptides, shielding of pathogen-associated molecular patterns, and inactivation of antifungal drugs. We found that certain strains of C. auris , predominantly from Clade I and IV, oxidized catecholamines into melanin pigment. The formation of this melanin occurred extracellularly, resulting in granule-like melanin structures that are deposited on the surface of the fungus. This melanization was primarily chemically driven and mediated by alkalinization of the extracellular environment. The C. auris strains had relatively high cell surface hydrophobicity, but we did not find a correlation between hydrophobicity and ability to melanize. Melanin protected the fungus from oxidative damage but we did not observe a protective role in vitro or in vivo during infection of macrophages or Galleria mellonella, respectively. In summary, C. auris alkalinizes the extracellular medium, which promotes the chemical autooxidation of the L-DOPA to melanin that then attaches to its surface, thus illustrating a different mechanism for fungal melanization.

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Candida Glabrata Produces a Melanin-Like Pigment that Protects Against Stress Conditions Encountered During Parasitism

Cited by 9 publications

References 33 publications

Comparative Biophysical and Ultrastructural Analysis of Melanins Produced by Clinical Strains of Different Species From the Trichosporonaceae Family

Comparative Biophysical and Ultrastructural Analysis of Melanins Produced by Clinical Strains of Different Species From the Trichosporonaceae Family

Melanization of Candida auris Is Associated with Alteration of Extracellular pH

Melanization ofCandida aurisis Associated with Alteration of Extracellular pH

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