Departamento de Microbiología y Parasitología-IRYCIS, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza de Ramón y Cajal s/n, E-28040, Madrid, Spain.
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208 |, 4200-135, Porto, Portugal.
Int Microbiol. 2020 Jan;23(1):23-29. doi: 10.1007/s10123-019-00069-1. Epub 2019 Mar 14.
In 1993, Brewster and Gustin described the existence of a kinase whose activity was essential for Saccharomyces cerevisiae to grow in environments with high osmolarity. This led to the discovery of the HOG pathway, a MAP kinase (MAPK) pathway that has been revealed to be crucial to respond to a wide range of stress conditions frequently encountered by fungi in their common habitats. MAPK signaling is initiated at the plasma membrane, where triggering stimuli lead to a phosphorylation cascade that ultimately activates transcription factors to ensure an appropriate adaptive response. In pathogenic fungi, the HOG pathway gains special significance as it is involved in traits related to pathogenicity; these include biofilm formation, adhesion to surfaces, and morphogenetic and epigenetic transitions. It also plays a role in controlling both the pathogen and the commensal state program. Understanding the signals leading to its activation, the elements of the pathways and the targets of the pathway are therefore of primary importance in the design of novel antifungals.
1993 年，Brewster 和 Gustin 描述了一种激酶的存在，其活性对酿酒酵母在高渗透压环境中生长至关重要。这导致了 HOG 途径的发现，这是一种丝裂原激活蛋白激酶 (MAPK) 途径，已被证明对真菌在其常见栖息地经常遇到的各种应激条件的反应至关重要。MAPK 信号在质膜起始，触发刺激导致磷酸化级联反应，最终激活转录因子以确保适当的适应性反应。在致病性真菌中，HOG 途径具有特殊意义，因为它与致病性相关的特性有关；这些特性包括生物膜形成、表面附着以及形态发生和表观遗传转变。它还在控制病原体和共生状态程序中发挥作用。因此，了解导致其激活的信号、途径的组成部分以及途径的靶点，对于设计新型抗真菌药物至关重要。
