Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
LabExperts sp. z o.o., Gdańsk, Poland.
Sci Rep. 2021 Feb 17;11(1):3959. doi: 10.1038/s41598-021-83632-z.
Keratin is important and needed for the growth of dermatophytes in the host tissue. In turn, the ability to invade keratinised tissues is defined as a pivotal virulence attribute of this group of medically important fungi. The host-dermatophyte interaction is accompanied by an adaptation of fungal metabolism that allows them to adhere to the host tissue as well as utilize the available nutrients necessary for their survival and growth. Dermatophyte infections pose a significant epidemiological and clinical problem. Trichophyton rubrum is the most common anthropophilic dermatophyte worldwide and its typical infection areas include skin of hands or feet and nail plate. In turn, Microsporum canis is a zoophilic pathogen, and mostly well known for ringworm in pets, it is also known to infect humans. The aim of the study was to compare the intracellular metabolite content in the T. rubrum and M. canis during keratin degradation using liquid chromatography system coupled with tandem mass spectrometer (LC-MS/MS). The metabolite "fingerprints" revealed compounds associated with amino acids metabolism, carbohydrate metabolism related to the glycolysis and the tricarboxylic acid cycle (TCA), as well as nucleotide and energy metabolism. The metabolites such as kynurenic acid, L-alanine and cysteine in case of T. rubrum as well as cysteine and riboflavin in case of M. canis were detected only during keratin degradation what may suggest that these compounds may play a key role in the interactions of T. rubrum and M. canis with the host tissue. The metabolomic results were completed by qPCR gene expression assay. Our findings suggest that metabolomic analysis of T. rubrum and M. canis growing in culture media that mimic the dermatophyte infection could allow the understanding of processes involved in the pathogenesis of dermatophytes.
角蛋白对亲角质真菌在宿主组织中的生长很重要。亲角质组织的侵袭能力是这群医学上重要的真菌的关键毒力特征。宿主-真菌相互作用伴随着真菌代谢的适应,使它们能够黏附在宿主组织上,并利用生存和生长所需的可用营养物质。皮肤癣菌感染构成了重大的流行病学和临床问题。红色毛癣菌是全球最常见的亲角质性皮肤癣菌,其典型感染部位包括手部或脚部皮肤和指甲板。相反,犬小孢子菌是一种亲动物性病原体,主要以宠物体癣而闻名,也已知会感染人类。本研究旨在使用液相色谱系统与串联质谱联用 (LC-MS/MS) 比较红色毛癣菌和犬小孢子菌在角蛋白降解过程中的细胞内代谢物含量。代谢物“指纹”揭示了与氨基酸代谢、与糖酵解和三羧酸循环 (TCA) 相关的碳水化合物代谢以及核苷酸和能量代谢相关的化合物。在红色毛癣菌中,如犬尿酸、L-丙氨酸和半胱氨酸,以及在犬小孢子菌中,如半胱氨酸和核黄素等代谢物仅在角蛋白降解过程中被检测到,这表明这些化合物可能在红色毛癣菌和犬小孢子菌与宿主组织的相互作用中发挥关键作用。代谢组学结果通过 qPCR 基因表达测定得到补充。我们的研究结果表明,在模拟皮肤癣菌感染的培养基中对红色毛癣菌和犬小孢子菌进行代谢组学分析,可以帮助理解皮肤癣菌发病机制中涉及的过程。