LaeA, a Regulator of Morphogenetic Fungal Virulence Factors

Abstract

ABSTRACT Opportunistic animal and plant pathogens, well represented by the genus Aspergillus , have evolved unique mechanisms to adapt to and avoid host defenses. Aspergillus fumigatus , an increasingly serious pathogen owing to expanding numbers of immunocompromised patients, causes the majority of human infections; however, an inability to identify bona fide virulence factors has impeded therapeutic advances. We show that an A. fumigatus mutation in a developmentally expressed transcriptional regulator ( ΔlaeA ) coordinating morphological and chemical differentiation reduces virulence in a murine model; impaired virulence is associated with decreased levels of pulmonary gliotoxin and multiple changes in conidial and hyphal susceptibility to host phagocytes ex vivo. LaeA, a conserved protein in filamentous fungi, is a developmental regulator of virulence genes and, possibly, the first antimicrobial target specific to filamentous fungi that are pathogenic to plants and animals.