Leister Kai, Dong Yan, Landmark Alexander, Ma Yinyan, Schreckenberger Birgit, Yu Zhenzhong, Lu Ling, Fischer Reinhard
Department of Microbiology, Institute for Applied Biosciences, Karlsruhe Institute of Technology (KIT)-South Campus, Karlsruhe, Germany.
Department of Clinical Laboratory, Nanjing Drum Tower Hospital, College of Life Sciences, Nanjing Normal University, Nanjing, China.
mBio. 2025 Sep 23:e0220425. doi: 10.1128/mbio.02204-25.
Phytochromes are red-light receptors that regulate gene expression in response to light and temperature in plants, bacteria, and fungi. In the opportunistic pathogenic fungus , two putative phytochromes-FphA and FphB-were characterized to assess any roles in virulence. Spectroscopic analysis of -expressed proteins showed that FphA is photoconvertible and functionally similar to its ortholog, whereas FphB is photoinactive. Therefore, only FphA could rescue an -deletion mutant. Gene deletion in revealed that loss of FphA had no effect on virulence, while deletion of FphB-alone or with FphA-significantly increased virulence in a infection model. Transcriptomic data linked FphB to the regulation of the neosartoricin B biosynthetic gene cluster and the production of the prenylated nonribosomal peptide hexadehydroastechrome, suggesting a role in regulating secondary metabolism. Localization studies showed FphA at the mitochondria and in nuclei and FphB mainly in the cytoplasm; both proteins form heterodimers in the cytoplasm and in nuclei. These findings suggest that while FphA acts as a light and temperature sensor, FphB modulates virulence and may represent a novel regulatory factor in fungal pathogenicity.IMPORTANCE is a major pathogen in immunocompromised individuals, showing greater virulence than despite genetic similarities. A key difference is the presence of two phytochrome-like proteins: FphA, a conserved red-light and temperature sensor, and FphB, a photoinactive hybrid histidine kinase. Notably, FphB appears to suppress virulence, suggesting a regulatory role in signaling pathways that govern pathogenicity and secondary metabolism. We propose FphB functions as a signaling hub linking environmental cues to virulence, with its network offering a promising target for antifungal strategies.
光敏色素是一种红光受体，可响应植物、细菌和真菌中的光照和温度来调节基因表达。在机会性致病真菌中，对两种假定的光敏色素——FphA和FphB进行了表征，以评估它们在毒力方面的任何作用。对表达的蛋白质进行光谱分析表明，FphA具有光转换能力，并且在功能上与其直系同源物相似，而FphB没有光活性。因此，只有FphA能够挽救一个缺失突变体。在该真菌中进行基因缺失研究表明，FphA的缺失对毒力没有影响，而单独缺失FphB或与FphA一起缺失，在感染模型中会显著增加毒力。转录组数据将FphB与新萨托菌素B生物合成基因簇的调控以及异戊烯化非核糖体肽十六脱氢曲霉色原酮的产生联系起来，表明其在调节次级代谢中发挥作用。定位研究表明，FphA存在于线粒体和细胞核中，而FphB主要存在于细胞质中；这两种蛋白质在细胞质和细胞核中形成异源二聚体。这些发现表明，虽然FphA作为光和温度传感器发挥作用，但FphB调节毒力，可能代表真菌致病性中的一种新型调节因子。重要性：该真菌是免疫功能低下个体中的主要病原体，尽管基因相似，但显示出比另一种真菌更强的毒力。一个关键差异是存在两种类光敏色素蛋白：FphA，一种保守的红光和温度传感器，以及FphB，一种无光活性的杂合组氨酸激酶。值得注意的是，FphB似乎抑制毒力，表明其在控制致病性和次级代谢的信号通路中发挥调节作用。我们提出FphB作为一个信号枢纽，将环境线索与毒力联系起来，其网络为抗真菌策略提供了一个有前景的靶点。
