Smith Daniel F Q, Mudrak Nathan J, Zamith-Miranda Daniel, Honorato Leandro, Nimrichter Leonardo, Chrissian Christine, Smith Barbara, Gerfen Gary, Stark Ruth E, Nosanchuk Joshua D, Casadevall Arturo
W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Krieger School of Arts & Science, Johns Hopkins University, Baltimore, MD 21218, USA.
J Fungi (Basel). 2022 Oct 11;8(10):1068. doi: 10.3390/jof8101068.
is a recently emerged global fungal pathogen, which causes life-threatening infections, often in healthcare settings. infections are worrisome because the fungus is often resistant to multiple antifungal drug classes. Furthermore, forms durable and difficult to remove biofilms. Due to the relatively recent, resilient, and resistant nature of , 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 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. 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 larvae. In summary, 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.
是一种最近出现的全球真菌病原体，常导致危及生命的感染，通常发生在医疗机构中。其感染令人担忧，因为这种真菌往往对多种抗真菌药物类别具有抗性。此外，它会形成持久且难以去除的生物膜。由于其相对较新出现、具有弹性且具有抗性的特性，我们研究了它是否产生常见的真菌毒力因子黑色素。黑色素是一种黑褐色色素，通常在芳香族前体的酶促氧化后产生，它通过抗氧化应激、逃避哺乳动物免疫反应以及使抗真菌肽和药物失活来促进真菌毒力。我们发现某些菌株能将L - 多巴和儿茶酚胺氧化成黑色素。黑色素化在细胞外由细胞外环境碱化介导的过程中发生，形成附着在真菌外表面的颗粒状结构。该真菌具有相对较高的细胞表面疏水性，但疏水性与黑色素化之间没有相关性。黑色素保护真菌免受氧化损伤，但在巨噬细胞或幼虫感染期间我们未观察到其保护作用。总之，该真菌使细胞外培养基碱化，这促进了L - 多巴非酶氧化成附着在其表面的黑色素，从而阐明了真菌黑色素化的一种新机制。
