The skin of humans and animals is colonized by commensal and pathogenic fungi and bacteria that share this ecological niche and have established microbial interactions. Malassezia are the most abundant fungal skin inhabitant of warm-blooded animals and have been implicated in skin diseases and systemic disorders, including Crohn’s disease and pancreatic cancer. Flavohemoglobin is a key enzyme involved in microbial nitrosative stress resistance and nitric oxide degradation. Comparative genomics and phylogenetic analyses within the Malassezia genus revealed that flavohemoglobin-encoding genes were acquired through independent horizontal gene transfer events from different donor bacteria that are part of the mammalian microbiome. Through targeted gene deletion and functional complementation in Malassezia sympodialis, we demonstrated that bacterially derived flavohemoglobins are cytoplasmic proteins required for nitric oxide detoxification and nitrosative stress resistance under aerobic conditions. RNA-sequencing analysis revealed that endogenous accumulation of nitric oxide resulted in up-regulation of genes involved in stress response and down-regulation of the MalaS7 allergen-encoding genes. Solution of the high-resolution X-ray crystal structure of Malassezia flavohemoglobin revealed features conserved with both bacterial and fungal flavohemoglobins. In vivo pathogenesis is independent of Malassezia flavohemoglobin. Lastly, we identified an additional 30 genus- and species-specific horizontal gene transfer candidates that might have contributed to the evolution of this genus as the most common inhabitants of animal skin.

人类和动物的皮肤被共有的，致病的真菌和细菌殖民，这些真菌和细菌共享这种生态位并建立了微生物相互作用。马拉色霉菌是温血动物中最丰富的真菌皮肤居民，与皮肤病和全身性疾病有关，包括克罗恩氏病和胰腺癌。黄素血红蛋白是参与微生物抗亚硝化应激和一氧化氮降解的关键酶。马拉色菌内的比较基因组学和系统发育分析属揭示黄素血红蛋白编码基因是通过来自不同供体细菌的独立水平基因转移事件而获得的，这些供体细菌是哺乳动物微生物组的一部分。通过有针对性的基因缺失和功能互补在马拉色sympodialis，我们表明，细菌来源flavohemoglobins是在有氧条件下的一氧化氮解毒和亚硝化应激抗性所需的胞质蛋白。RNA测序分析显示，一氧化氮的内源性积累导致与应激反应有关的基因上调，而MalaS7过敏原编码基因下调。马拉色菌属的高分辨率X射线晶体结构的解决方案黄素血红蛋白揭示了细菌和真菌黄素血球蛋白均保守的特征。体内发病机理独立于马拉色黄素血红蛋白。最后，我们确定了另外30个属和种特定的水平基因转移候选物，这些候选物可能是该属作为动物皮肤最常见的种群而进化的原因。