Melanin: Quantification and protection against oxidative stress in chromoblastomycosis agents

Heidrich, Daiane; Corbellini, Valeriano Antônio; Mendes, Sandra Denise Camargo; Fernandes, Elissa Kerli; Lazzarotto, Letícia; Ribeiro, Amanda Carvalho; Zanette, Régis A.; Scroferneker, Maria Lúcia

doi:10.1093/mmy/myy013

Cited by 11 publications

(8 citation statements)

References 11 publications

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“…To determine whether the process of melanization elicits changes in cell-wall composition, we examined cells from the three strains, each grown in the presence and absence of L-DOPA. Since melanin pigments have been reported previously to comprise only a minor fraction (1–15.4%) of the total dry mass of melanizing fungal cells [ 50 , 51 ] and are likely to have large molar masses, the NMR signals that arise from pigment carbons make a negligible contribution to the overall spectral intensity. Consequently, we were able to make quantitative estimates of relative polysaccharide content regardless of whether melanin was present.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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show abstract

“…To determine whether the process of melanization elicits changes in cell-wall composition, we examined cells from the three strains, each grown in the presence and absence of L-DOPA. Since melanin pigments have been reported previously to comprise only a minor fraction (1-15.4%) of the total dry mass of melanizing fungal cells (44,45) and are likely to have large molar masses, the NMR signals that arise from pigment carbons make a negligible contribution to the overall spectral intensity. Consequently, we were able to make quantitative estimates of relative polysaccharide content regardless of whether melanin was present.…”

Section: Resultsmentioning

confidence: 99%

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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“…This suggests that gravimetric analysis is adequate to quantify DHN‐melanin, as the small expected result in the condition of hypopigmentation has been achieved [9]. This same method was used by Heidrich et al [34], who carried out a study with the five main genera of CBM agents. In this study, the average percentage of melanin mass extracted from the dry fungal with mass ranged from 0.69% ( Rhinocladiella similis ) to 3.81% ( Phialophora americana ), showing that its quantification is variable among the main fungi that cause CBM.…”

Section: Qualitative and Quantitative Analysismentioning

confidence: 99%

“…In a more comprehensive study, conducted in 2018 with 77 strains of CBM agents, distributed in five different genera, it was found that melanin conferred protection against oxidative stress in all isolates. In general, the degree of protection was proportional to the amount of melanin that each species produces, however it is possible that there are other protective factors in addition to this compound [34].…”

Section: Structural and Antioxidant Functionsmentioning

confidence: 99%

Melanin and chromoblastomycosis agents: Characterization, functions, and relation with antifungals

et al. 2021

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Melanins are a diverse group of dark pigments with similar properties. In fungi, the most studied is the dihydroxynaphtalene (DHN)‐melanin, present in several species including all the chromoblastomycosis agents, a chronic, disabling, and recalcitrant subcutaneous mycosis. It is synthesized in a pathway known as the pentaketide pathway, which has the agrochemical tricyclazole as an inhibitor, widely used in in vitro studies because it does not prevent the growth of fungi. There are different methodologies for qualitative and quantitative analyses of DHN‐melanin, which made it possible to discover its important structural and antioxidant functions, with melanin acting as a protective factor against the host's immune system. Also, it can interact with some of the main antifungals of medical interest, reducing its activity and the susceptibility of fungi to these agents. This review aims to discuss the aspects of DHN‐melanin, focusing on chromoblastomycosis, bringing the main findings of the published scientific studies, and highlighting the need for further research to understand this important fungal pathogenicity and a virulence factor.

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Melanin: Quantification and protection against oxidative stress in chromoblastomycosis agents

Cited by 11 publications

References 11 publications

Melanization of Candida auris Is Associated with Alteration of Extracellular pH

Melanization of Candida auris Is Associated with Alteration of Extracellular pH

Melanization ofCandida aurisis Associated with Alteration of Extracellular pH

Melanin and chromoblastomycosis agents: Characterization, functions, and relation with antifungals

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