AUTHOR=Wijnants Stefanie , Riedelberger Michael , Penninger Philipp , Kuchler Karl , Van Dijck Patrick 

TITLE=Sugar Phosphorylation Controls Carbon Source Utilization and Virulence of Candida albicans

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01274

DOI=10.3389/fmicb.2020.01274

ISSN=1664-302X

ABSTRACT=<p><italic>Candida albicans</italic> 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 <italic>C. albicans</italic>. Sequence comparison with <italic>Saccharomyces cerevisiae</italic> identified four enzymes (Hxk1, Hxk2, Glk1, and Glk4) in <italic>C. albicans</italic> 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 <italic>HXK2</italic>, <italic>GLK1</italic>, and <italic>GLK4</italic> 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 <italic>HXK1</italic> decreases biofilm formation. Finally, we demonstrate that <italic>hxk2Δ</italic>/<italic>Δ glk1Δ/Δ glk4Δ/Δ</italic> and <italic>hxk1Δ/Δ hxk2Δ/Δ glk1Δ/Δ glk4Δ/Δ</italic> 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 <italic>C. albicans</italic> relies on a functional glycolytic pathway for maximal virulence.</p>