LaeA, a regulator of morphogenetic fungal virulence factors.
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 (deltalaeA) 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.
Bok
Jin Woo
JW
University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Balajee
S Arunmozhi
SA
Marr
Kieren A
KA
Andes
David
D
Nielsen
Kristian Fog
KF
Frisvad
Jens C
JC
Keller
Nancy P
NP
D000328:Adult; D000818:Animals; D001232:Aspergillus fumigatus / Q000235:genetics* / Q000472:pathogenicity*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000502:physiology*; D005912:Gliotoxin / Q000378:metabolism; D006801:Humans; D025301:Hyphae / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation / Q000235:genetics*; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000502:physiology*
D037521:Virulence Factors; D005912:Gliotoxin