Candida glabrata subverts intracellular trafficking and modulates autophagy to replicate in human epithelial cells.

In recent years, Candida glabrata (C. glabrata) has emerged as a pathogen responsible for systemic mortal infections. C. glabrata invades nonphagocytic cells, but the mechanisms involved in its internalization and its intracellular fate in these cells remain poorly understood. Here, it was shown that endocytosis of C. glabrata in epithelial cells partially depends on actin and microtubule rearrangements; importantly, C. glabrata promotes its uptake. The analysis of intracellular fate determined that C. glabrata avoids the fusion of endocytic vacuoles with lysosomes and replicates in epithelial cells. Additionally, C. glabrata downregulates host cell autophagy in the first hour of infection, which correlates with its intracellular replication. Remarkably, the ectopic activation of autophagy contributed to the control of intracellular growth of this yeast. These findings highlight the ability of C. glabrata to manipulate host proteins involved in endocytic processes and intracellular trafficking. Likewise, these results suggest a strong role of host autophagy in controlling fungal pathogens such as C. glabrata.