<i>Candida albicans</i> Goliath cells pioneer biofilm formation

<i>Candida albicans</i> is a fungal pathogen that can cause life-threatening bloodstream infections. Indwelling medical devices, such as catheters, play a critical role in their progression, as <i>C. albicans</i> can colonize these devices and form biofilms, which can then seed the bloodstream, resulting in recurrent candidemia. Under conditions of zinc restriction, <i>C. albicans</i> forms enlarged Goliath cells. Here, we show that Goliath cells exhibit enhanced adhesion to host tissue under static conditions, particularly to vaginal and oral epithelial cell monolayers. Moreover, Goliath cells are fully capable of forming hyphae and damaging host tissue. Notably, the adhesion of Goliath cells to abiotic surfaces surpasses their adhesion to epithelia or endothelia, suggesting that Goliath cells may possess a unique advantage in colonizing indwelling medical devices, such as catheters within the circulatory system. We also show that the cell wall of Goliath cells has increased hydrophobicity compared with yeasts. In microfluidic channels mimicking the shear stress present in the circulatory system, yeast cells exhibit negligible adhesion to plastic surfaces, even at minimal flow rates. In contrast, Goliath cells demonstrate robust adherence to abiotic surfaces, maintaining attachment even under supraphysiological shear stress conditions. We show that biofilms formed by Goliath cells are more metabolically active and structurally denser in terms of the volume of hyphae. A high number of adhesive "pioneer" Goliath cells in the base of the biofilm significantly affects their architecture and anchors them to abiotic surfaces. These insights into Goliath cells' pathogenicity shed light on their potential role in colonization of medical devices.IMPORTANCEGoliath cells, known for their large size and stickiness to plastic, are triggered by limited access to the essential mineral zinc. They are a specialized cell type of <i>Candida albicans</i>, a fungus that causes skin, oral, and vaginal yeast infections as well as severe bloodstream infections. Medical devices like catheters can make these bloodstream infections worse because <i>Candida</i> forms biofilms on them, which results in continuous seeding of fungal cells into the bloodstream. We found that Goliath cells adhere to vaginal and oral tissue better than normal yeast cells. Surprisingly, they stick even better to abiotic surfaces than to mammalian cells. This suggests they might have an advantage in attaching to catheters during <i>Candida</i> bloodstream infection. When we simulated blood flow, regular yeast cells did not stick to plastic surfaces, but Goliath cells attach even at very high flow rates. This allowed them to form much thicker and active biofilms on these surfaces. Understanding how Goliath cells work can help us figure out better ways to prevent and treat infections caused by <i>Candida albicans</i>, especially those related to medical devices like catheters.