Global Control of Dimorphism and Virulence in Fungi

TLDR

Six dimorphic fungi that normally exist as soil molds switch to pathogenic yeasts in mammals, but the regulatory mechanisms of this transition remain poorly understood. A hybrid histidine kinase that senses host signals drives the mold‑to‑yeast switch, controls cell‑wall integrity, sporulation, and virulence gene expression, and thus globally regulates dimorphic fungal adaptation to mammals, offering new therapeutic targets.

Abstract

Microbial pathogens that normally inhabit our environment can adapt to thrive inside mammalian hosts. There are six dimorphic fungi that cause disease worldwide, which switch from nonpathogenic molds in soil to pathogenic yeast after spores are inhaled and exposed to elevated temperature. Mechanisms that regulate this switch remain obscure. We show that a hybrid histidine kinase senses host signals and triggers the transition from mold to yeast. The kinase also regulates cell-wall integrity, sporulation, and expression of virulence genes in vivo. This global regulator shapes how dimorphic fungal pathogens adapt to the mammalian host, which has broad implications for treating and preventing systemic fungal disease.