Wijnants Stefanie, Riedelberger Michael, Penninger Philipp, Kuchler Karl, Van Dijck Patrick
Laboratory of Molecular Cell Biology, Department of Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium.
VIB-KU Leuven Center for Microbiology, Leuven, Belgium.
Front Microbiol. 2020 Jun 16;11:1274. doi: 10.3389/fmicb.2020.01274. eCollection 2020.
is an opportunistic human fungal pathogen that relies upon different virulence traits, including morphogenesis, invasion, biofilm formation, and nutrient acquisition from host sources as well as metabolic adaptations during host invasion. In this study, we show how sugar kinases at the start of glycolysis modulate virulence of . Sequence comparison with identified four enzymes (Hxk1, Hxk2, Glk1, and Glk4) in with putative roles in sugar phosphorylation. Hxk2, Glk1, and Glk4 demonstrate a critical role in glucose metabolism, while Hxk2 is the only kinase important for fructose metabolism. Additionally, we show that Hxk1 controls , , and expression in the presence of fermentable as well as non-fermentable carbon sources, thereby indirectly controlling glycolysis. Moreover, these sugar kinases are important during virulence. Disabling the glycolytic pathway reduces adhesion capacity, while deletion of decreases biofilm formation. Finally, we demonstrate that / and have attenuated virulence upon systemic infections in mice. These results indicate a regulatory role for Hxk1 during sugar phosphorylation. Furthermore, these kinases are essential during growth on glucose or fructose, and relies on a functional glycolytic pathway for maximal virulence.
是一种机会性人类真菌病原体，它依赖于不同的毒力特征，包括形态发生、侵袭、生物膜形成、从宿主来源获取营养以及在宿主侵袭期间的代谢适应。在本研究中，我们展示了糖酵解起始阶段的糖激酶如何调节的毒力。与的序列比较在中鉴定出四种在糖磷酸化中具有推定作用的酶（Hxk1、Hxk2、Glk1和Glk4）。Hxk2、Glk1和Glk4在葡萄糖代谢中起关键作用，而Hxk2是果糖代谢中唯一重要的激酶。此外，我们表明Hxk1在可发酵和不可发酵碳源存在的情况下控制、和的表达，从而间接控制糖酵解。而且，这些糖激酶在毒力过程中很重要。使糖酵解途径失活会降低黏附能力，而缺失会减少生物膜形成。最后，我们证明/和在小鼠全身感染后毒力减弱。这些结果表明Hxk1在糖磷酸化过程中具有调节作用。此外，这些激酶在葡萄糖或果糖上生长期间至关重要，并且依赖于功能性糖酵解途径以实现最大毒力。
