Koroleva Elizaveta, Toplis Barbra, Taylor Malcolm, van Deventer Corné, Steffen Heidi C, van den Heever Christiaan, Govender Nelesh P, de Hoog Sybren, Botha Alfred
Department of Microbiology, University of Stellenbosch, Stellenbosch, 7600, South Africa.
Mass Spectrometry Unit, Central Analytical Facility, University of Stellenbosch, Stellenbosch, 7600, South Africa.
FEMS Yeast Res. 2024 Jan 9;24. doi: 10.1093/femsyr/foae038.
Emergomyces africanus is a thermally dimorphic pathogen causing severe morbidity and mortality in immunocompromized patients. Its transition to a pathogenic yeast-like phase in the human host is a notable virulence mechanism. Recent studies suggest polyamines as key players in dimorphic switching, yet their precise functions remain enigmatic. This work aimed to explore polyamine metabolism of two clinical strains of E. africanus (CBS 136260 and CBS 140360) in mycelial and yeast-like phases. In this first report of the polyamine profile of E. africanus, we reveal, using mass spectrometry, spermidine, and spermine as the major polyamines in both phases. The secretion of these amines was significantly higher in the pathogenic yeast-like phase than in the mycelial phase, warranting further investigation into the implications thereof on virulence. Additionally, we detected the activity of several polyamine biosynthesis enzymes, including arginine decarboxylase, agmatinase, arginase, and ornithine decarboxylase, with significant differences in enzyme expression between morphological phases and strains. Finally, we provide initial evidence for the requirement for spermine, spermidine, and putrescine during the thermally induced dimorphic switch of E. africanus, with strain-specific differences in the production of these amines. Overall, our study presents novel insight into polyamine metabolism and its role in dimorphism of E. africanus.
非洲埃默热孢霉是一种温度双态性病原体,可导致免疫功能低下患者出现严重发病和死亡。它在人类宿主中转变为致病性酵母样阶段是一种显著的毒力机制。最近的研究表明多胺是双态转换的关键因素,但其确切功能仍不清楚。这项工作旨在探索非洲埃默热孢霉的两个临床菌株(CBS 136260和CBS 140360)在菌丝体阶段和酵母样阶段的多胺代谢。在这份关于非洲埃默热孢霉多胺谱的首次报告中,我们通过质谱分析发现,亚精胺和精胺是两个阶段的主要多胺。这些胺类在致病性酵母样阶段的分泌显著高于菌丝体阶段,因此有必要进一步研究其对毒力的影响。此外,我们检测了几种多胺生物合成酶的活性,包括精氨酸脱羧酶(arginine decarboxylase)、胍丁胺酶(agmatinase)、精氨酸酶(arginase)和鸟氨酸脱羧酶(ornithine decarboxylase),形态阶段和菌株之间的酶表达存在显著差异。最后,我们提供了初步证据,证明非洲埃默热孢霉在热诱导双态转换过程中需要精胺、亚精胺和腐胺,且这些胺类的产生存在菌株特异性差异。总体而言,我们的研究为多胺代谢及其在非洲埃默热孢霉双态性中的作用提供了新的见解。