Cinnamomum zeylanicum bark essential oil induces cell wall remodelling and spindle defects in Candida albicans

Zinnat Shahina, Amira M. El-Ganiny, Jessica Minion, Malcolm Whiteway, Taranum Sultana, Tanya E. S. Dahms

Cinnamon (Cinnamomum zeylanicum)bark extract exhibits potent inhibitory activity againstCandida albicansbut the antifungal mechanisms of this essential oil remain largely unexplored. We analyzed the impact of cinnamon bark oil onC. albicansRSY150, and clinical strains isolated from patients with candidemia and candidiasis. The viability of RSY150 was significantly compromised in a dose dependent manner when exposed to cinnamon bark oil, with extensive cell surface remodelling at sub inhibitory levels (62.5 μg/mL). Atomic force microscopy revealed cell surface exfoliation, altered ultrastructure and reduced cell wall integrity for both RSY150 and clinical isolates exposed to cinnamon bark oil. Cell wall damage induced by cinnamon bark oil was confirmed by exposure to stressors and the sensitivity of cell wall mutants involved in cell wall organization, biogenesis, and morphogenesis. The essential oil triggered cell cycle arrest by disrupting beta tubulin distribution, which led to mitotic spindle defects, ultimately compromising the cell membrane and allowing leakage of cellular components. The multiple targets of cinnamon bark oil can be attributed to its components, including cinnamaldehyde (74%), and minor components (< 6%) such as linalool (3.9%), cinamyl acetate (3.8%), α-caryophyllene (5.3%) and limonene (2%). Complete inhibition of the mitotic spindle assembly was observed inC. albicanstreated with cinnamaldehyde at MIC (112 μg/mL). Since cinnamaldehyde disrupts both the cell wall and tubulin polymerization, it may serve as an effective antifungal, either by chemical modification to improve its specificity and efficacy or in combination with other antifungal drugs.