A mathematical model captures the role of adenyl cyclase Cyr1 and guanidine exchange factor Ira2 in creating a growth‐to‐hyphal bistable switch in Candida albicans

Abstract

Recent biochemical experiments have indicated that in Candida albicans, a commensal fungal pathogen, the Ras signaling pathway plays a significant role in the yeast‐to‐hyphal transition; specifically, two enzymes in this pathway, Adenyl Cyclase Cyr1 and GTPase activating protein Ira2, facilitate this transition, in the presence of energy sensor ATP. However, the precise mechanism by which protein interactions between Ira2 and Cyr1 and the energy sensor ATP result in the yeast‐to‐hyphal transition and create a switch‐like process are unknown. We propose a new set of biochemical reaction steps that captures all the essential interactions between Ira2, Cyr1, and ATP in the Ras pathway. With the help of chemical reaction network theory, we demonstrate that this set of biochemical reaction steps results in bistability. Further, bifurcation analysis of the differential equations based on this set of reaction steps supports the existence of a bistable switch, and this switch may act as a checkpoint mechanism for the promotion of growth‐to‐hyphal transition in C. albicans.

Keywords

• bistable
• Candida albicans
• ODE
• positive feedback
• Ras signaling pathway
• yeast‐hyphal switching