Liporagi-Lopes Livia C, Chrissian Christine, Kacirani Arlind, Camacho Emma, Stark Ruth E, Casadevall Arturo
Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Current Address: Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
bioRxiv. 2024 Nov 1:2024.11.01.621558. doi: 10.1101/2024.11.01.621558.
is a filamentous fungus with a global distribution, manifesting particularly higher prevalence in human-impacted environments. This organism is associated with a wide spectrum of human infections, especially in immunosuppressed individuals, for whom it causes severe and debilitating illnesses with high morbidity and mortality that are compounded by its pan-resistant profile with respect to antifungal drugs. Melanin is a ubiquitous pigment among fungi with a broad range of actions that include promoting fungal virulence. Although melanin is one of the most studied virulence factors in pathogenic fungi, relatively little is known about the chemistry of this pigment in In the current study we characterized -associated melanin using chemical, biological, biophysical and structural techniques, also assessing the impact of inhibitors of distinct melanization pathways. Our results reveal that this pathogenic fungus makes multiple types of melanin pigments and suggests the possibility of a new type of melanin, which is synthesized together with a mixture of DHN-, DOPA- and pyomelanin types. These insights enhance our understanding of virulence mechanisms, paving the way for potential therapeutic interventions.
是一种丝状真菌,分布于全球,在受人类影响的环境中尤其更为常见。这种生物体与多种人类感染相关,特别是在免疫抑制个体中,它会导致严重且使人衰弱的疾病,发病率和死亡率很高,而其对抗真菌药物的泛耐药性又加剧了这种情况。黑色素是真菌中普遍存在的一种色素,具有广泛的作用,包括促进真菌毒力。尽管黑色素是致病真菌中研究最多的毒力因子之一,但对于这种色素在[此处原文缺失相关真菌名称]中的化学性质了解相对较少。在当前研究中,我们使用化学、生物学、生物物理和结构技术对[此处原文缺失相关真菌名称]相关的黑色素进行了表征,还评估了不同黑色素化途径抑制剂的影响。我们的结果表明,这种致病真菌产生多种类型的黑色素色素,并提示存在一种新型黑色素的可能性,它是与二羟基萘(DHN)型、多巴型和棕黑素型的混合物一起合成的。这些见解加深了我们对[此处原文缺失相关真菌名称]毒力机制的理解,为潜在的治疗干预铺平了道路。